X
Search Filters
Format Format
Format Format
X
Sort by Item Count (A-Z)
Filter by Count
Journal Article (2661) 2661
Dissertation (751) 751
Book / eBook (488) 488
Publication (368) 368
Book Chapter (227) 227
Book Review (84) 84
Newsletter (24) 24
Conference Proceeding (17) 17
Newspaper Article (17) 17
Reference (17) 17
Report (9) 9
Data Set (1) 1
Magazine Article (1) 1
more...
Subjects Subjects
Subjects Subjects
X
Sort by Item Count (A-Z)
Filter by Count
index medicus (1515) 1515
animals (1000) 1000
humans (938) 938
proteins (835) 835
biochemistry & molecular biology (648) 648
molecular biology (588) 588
cell biology (547) 547
heat shock proteins (463) 463
microbiology (433) 433
immunology (415) 415
gene expression (396) 396
biochemistry (395) 395
analysis (390) 390
life sciences (379) 379
biology (362) 362
physiological aspects (355) 355
research (346) 346
genetics (339) 339
cancer (307) 307
genes (283) 283
amino acid sequence (279) 279
cellular biology (275) 275
molecular sequence data (275) 275
medicine (270) 270
signal transduction (255) 255
plant sciences (244) 244
genetic aspects (242) 242
research article (242) 242
article (241) 241
physiology (238) 238
protein binding (209) 209
science (206) 206
protein folding (199) 199
review (199) 199
escherichia-coli (196) 196
apoptosis (193) 193
biochemistry, general (193) 193
bacteria (191) 191
multidisciplinary sciences (190) 190
expression (188) 188
heat-shock proteins (183) 183
genomics (179) 179
molecular chaperones (176) 176
health aspects (175) 175
enzymes (173) 173
oncology (172) 172
mice (170) 170
genomes (169) 169
phylogeny (169) 169
biotechnology (165) 165
gene-expression (164) 164
oxidative stress (164) 164
biophysics (159) 159
protein (152) 152
biotechnology & applied microbiology (149) 149
crystal-structure (146) 146
pharmacology (146) 146
plants (144) 144
genetics & heredity (141) 141
metabolism (140) 140
mutation (139) 139
pharmacology & pharmacy (139) 139
chemistry (138) 138
gene expression regulation (138) 138
in-vivo (137) 137
biomedicine (136) 136
stress (135) 135
cells (134) 134
identification (133) 133
evolution (130) 130
rna (128) 128
fungi (126) 126
kinases (125) 125
models, molecular (124) 124
in-vitro (117) 117
nf-kappa-b (116) 116
arabidopsis-thaliana (114) 114
proteomics (113) 113
electronic books (112) 112
heat-shock proteins - metabolism (112) 112
toxicology (112) 112
saccharomyces-cerevisiae (111) 111
molecular chaperones - metabolism (108) 108
diseases (107) 107
immune response (107) 107
inflammation (107) 107
innate immunity (107) 107
chaperones (106) 106
heat-shock-protein (106) 106
hsp90 (106) 106
amino acids (105) 105
chaperone (104) 104
gene expression profiling (104) 104
models, biological (104) 104
pathogens (104) 104
phosphorylation (104) 104
protein structure, tertiary (104) 104
genetic research (100) 100
neurosciences (100) 100
hsp70 (99) 99
more...
Library Location Library Location
Library Location Library Location
X
Sort by Item Count (A-Z)
Filter by Count
Gerstein Science - Stacks (312) 312
Collection Dvlpm't (Acquisitions) - Closed Orders (61) 61
Collection Dvlpm't (Acquisitions) - Vendor file (46) 46
UofT at Mississauga - Stacks (44) 44
UofT at Scarborough - Stacks (32) 32
Online Resources - Online (26) 26
UTL at Downsview - May be requested (25) 25
Earth Sciences (Noranda) - Stacks (24) 24
Sunnybrook Health Sciences Centre - Sunnybrook Stacks (13) 13
St. Michael's Hospital - Stacks (11) 11
Scarborough Hospital - General (7) 7
Gerstein Science - Circulation Desk (6) 6
Gerstein Science - Reference (6) 6
Lakeridge Health Sciences - Oshawa (6) 6
Chemistry (A D Allen) - Stacks (5) 5
Media Commons - Microtexts (5) 5
Trinity College (John W Graham) - Stacks (5) 5
UofT at Mississauga - Reference (5) 5
Humber River Regional Hospital - Finch Stacks (4) 4
Scarborough Hospital - Birchmount (4) 4
Baycrest Hospital - Stacks (3) 3
Dentistry (Harry R Abbott) - May be requested in 6-10 wks (3) 3
Dentistry (Harry R Abbott) - Stacks (3) 3
Gerstein Science - Course Reserves (3) 3
Gerstein Science - Missing (3) 3
Humber River Regional Hospital - Church Stacks (3) 3
Providence Healthcare - Reference (3) 3
Providence Healthcare - Stacks (3) 3
St Josephs Health Centre - Stacks (3) 3
Credit Valley Hospital - Stacks (2) 2
Dentistry (Harry R Abbott) - Withdrawn (2) 2
Earth Sciences (Noranda) - Missing (2) 2
Engineering & Comp. Sci. - Reference (2) 2
Royal Ontario Museum - Stacks (2) 2
St. Michael's College (John M. Kelly) - 2nd Floor (2) 2
Trillium Health Centre - Stacks (2) 2
Baycrest Hospital - Course Reserves (1) 1
Collection Dvlpm't (Acquisitions) - Online (1) 1
Collection Dvlpm't (Acquisitions) - Reference (1) 1
Credit Valley Hospital - Reference (1) 1
Credit Valley Hospital - Reserve desk (1) 1
Earth Sciences (Noranda) - Circulation Desk (1) 1
Engineering & Comp. Sci. - Stacks (1) 1
Gerstein Science - Closed Orders (1) 1
Gerstein Science - May be requested (1) 1
Gerstein Science - May be requested in 6-10 wks (1) 1
Gerstein Science - Searching (1) 1
Humber River Regional Hospital - Church Reference (1) 1
Markham Stouffville Hospital - Stacks (1) 1
May be requested (1) 1
Media Commons - Microfiche (1) 1
Missing (1) 1
Physics - Stacks (1) 1
Scarborough Hospital - Closed Orders (1) 1
St Josephs Health Centre - General (1) 1
St Josephs Health Centre - Reference (1) 1
St. Michael's Hospital - Circulation Desk (1) 1
Stacks (1) 1
Sunnybrook Health Sciences Centre - Sunnybrook Reference (1) 1
Toronto East General Hospital - Online (1) 1
Toronto East General Hospital - Stacks (1) 1
Trillium Health Centre - Reserve desk (1) 1
Trinity College (John W Graham) - Reference (1) 1
UTL at Downsview - Pharmacy (1) 1
UofT at Mississauga - Closed Orders (1) 1
UofT at Mississauga - Missing (1) 1
UofT at Scarborough - May be requested in 6-10 wks (1) 1
UofT at Scarborough - Sunnybrook Stacks (1) 1
UofT at Scarborough - Withdrawn (1) 1
Victoria University E.J. Pratt - Circulation Desk (1) 1
Victoria University E.J. Pratt - Oversize (1) 1
Victoria University E.J. Pratt - Reference (1) 1
Victoria University E.J. Pratt - Stacks (1) 1
West Park Healthcare Centre - Stacks (1) 1
Women's College Hospital - Pharmacy (1) 1
Women's College Hospital - Stacks (1) 1
more...
Language Language
Language Language
X
Sort by Item Count (A-Z)
Filter by Count
English (4144) 4144
Spanish (54) 54
Arabic (7) 7
German (7) 7
Czech (5) 5
Portuguese (5) 5
Japanese (3) 3
Chinese (2) 2
French (2) 2
Italian (2) 2
Dutch (1) 1
Polish (1) 1
Turkish (1) 1
more...
Publication Date Publication Date
Click on a bar to filter by decade
Slide to change publication date range


Biomedical Journal, ISSN 2319-4170, 05/2013, Volume 36, Issue 3, pp. 106 - 117
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of... 
Hsp90 | conformational cycle | clients | posttranslational modifications | ATPase | co-chaperones | Animals | HSP90 Heat-Shock Proteins - antagonists & inhibitors | HSP90 Heat-Shock Proteins - physiology | Humans | HSP90 Heat-Shock Proteins - chemistry | Protein Conformation | Protein Processing, Post-Translational | Molecular Chaperones - physiology | Signal transduction | Antibiotics | Protein folding | Breast cancer | Kinases | Machinery | Binding sites | Hsp90 can be secreted as well and it promotes tumor invasiveness. Blocking the secreted Hsp90 led to a significant inhibition of tumor metastasis. Structure of Hsp90 Top Structurally | nucleotide binding is not the only determinant for Hsp90 conformation. The interaction with co-chaperones and client protein also influences the conformational rearrangement of Hsp90. | p23/Sba1 | eNOS | in which the ATP lid is closed but the N-domains are still open. The N-terminal dimerization leads to the formation of the second intermediate state (I2) | while Hsp90β is constitutively expressed. Hsp90 analogues also exist in other cellular compartments such as Grp94 in the endoplasmic reticulum | the M-domain contributes to the interaction sites for client proteins and some co-chaperones. The C-domain is essential for the dimerization of Hsp90. Interestingly | Hsp90 works together with a large group of cofactors | the activation of its client protein | MutL (GHKL) domain ATPases | Therefore | Binding of Aha1 induces a partially closed Hsp90 conformation and accelerates the progression of the ATPase cycle dramatically. | Different from other well-known molecular chaperone like Hsp70 and GroEL/ES | Interestingly | 113 | which acts as a core modulator in plant immunity. During the recruitment and activation of NLRs | more than 200 Hsp90 client proteins have been identified (see http://www.picard.ch/downloads/Hsp90interactors.pdf ). Besides the well-studied clients such as protein kinases and SHRs | 115 | termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90 | 116 | Our understanding of the Hsp90 machinery has been greatly advanced by research of the last decades. However | 118 | Function and Regulation of the Hsp90 Machinery. Biomed J 2013;36:106-17 How to cite this URL: Li J | leading to an asymmetric intermediate complex. Hsp90 adopts the ATPase-active (closed) conformation after binding of ATP. p23/Sba1 stabilizes the closed state of Hsp90 | and protein degradation. Interestingly | the lid segment is very flexible | and the NLR protein may dissociate from Hsp90. Hsp90 complexes in RNA processing Recent studies showed that Hsp90 is also involved in the assembly of small nucleolar ribonucleoproteins (snoRNPs) and RNA polymerase. | 15 | the lid segment promotes ATP hydrolysis. Once ATP is hydrolyzed | with 1 min–1 for yeast Hsp90 and 0.1 min–1 for human Hsp90. | hyperphosphorylation also leads to a decreased Hsp90 activity. In yeast | although a TPR domain is present in Sgt1 as well | California | Germany Date of Submission 05-Sep-2012 Date of Acceptance 02-Nov-2012 Date of Web Publication 10-Jun-2013 Correspondence Address: Johannes Buchner Center for Integrated Protein Science | the M-domain in blue | which weakens the binding of Hop/Sti1 and promotes its exit from the complex. Potentially another PPIase (dashed line) associates to form the "late complex" together with Hsp90 and p23/Sba1. After the hydrolysis of ATP | posttranslational modifications of Hsp90 | and protein degradation | 125 | 5 | the protein phosphatase PP5 (yeast homologue Ppt1) | 6 | in eukaryotic Hsp90 | such as mitochondrial/chloroplast protein import (Tom70/Toc64) | 9 | In Ppt1 knockout strains | posttranslational modifications How to cite this article: Li J | Hsp90 is a homodimer and each protomer contains three flexibly linked regions | p23 is a conformation-specific co-chaperone which binds exclusively to the closed conformation of Hsp90. | 24 | viral infection | 27 | Fkbp51 | They regulate the function of Hsp90 in different ways such as inhibition and activation of the ATPase of Hsp90 as well as recruitment of specific client proteins to the cycle. Interestingly | such as double-stranded DNA protein kinase | in which the ATP lid is closed but the N-domains are still open. Then | 132 | one of the most abundant and conserved molecular chaperones | and the C-domain in orange. Click here to view Conformational dynamics of Hsp90 Top Hsp90 is a weak ATPase and the turnover rates are very low | After fast ATP binding | Hsp90 adopts a "V"- shaped form | 35 | the maturation of protein kinases also requires the Hsp70 chaperone machinery [Figure 3]B. In the early stage | Research on the assembly of Hsp90 with SHRs had shown that several distinct complexes are formed during the maturation processes. | phosphorylation affects the conformational cycle of Hsp90 | Hsp90 stabilizes and promotes the correct folding of its client proteins | recent results imply that p53 may be destabilized by Hsp90 | and ch-Hsp90 in the chloroplast. | Chaperone cycle for protein kinases Similar to SHRs | 40 | 43 | the potentiation effects do not strictly depend on the PPIase activity of Fkbp52 as PPIase-deficient mutants are also able to potentiate GR transactivation | Technical University of Munich. Lichtenbergstrasse 4 | Notably | Nucleotide binding induces directionality and a conformational cycle. | 49 | similar heterocomplexes can be found from yeast to man even in the absence of client protein. Recent studies [using FRET | PPIase | Pih1 | co-chaperone interaction | Click here to view optimized website for mobile devices Journal is indexed with MEDLINE/Index Medicus and PubMed Share on facebookShare on twitter Share on citeulike Share on googleShare on linkedin More Sharing Services Table of Contents REVIEW ARTICLE Year : 2013 | Volume : 36 | Issue : 3 | Page : 106-117 Structure | while c-Src is largely independent of Hsp90. Notably | which implies that the tight regulation of the Hsp90 phosphorylation state is necessary for the efficient processing of client proteins. Chaperone cycle for nucleotide-binding site and leucine-rich repeat domain containing (NLR) proteins NLRs are conserved immune sensors which recognize pathogens. Accumulating evidence indicates that Hsp90 and its co-chaperones Sgt1 and Rar1 are involved in the maturation of these proteins. Sgt1 interacts with the N-domain of Hsp90 through its CS domain | acetylation | It is reasonable to assume that Hsp90 recognizes certain conformations or the stability of the client protein rather than its primary sequence. Src kinase is a prominent example here. The v-Src and its cellular counterpart (c-Src) share 95% sequence identity but distinct Hsp90 dependency. The activation of v-Src strictly depends on Hsp90 | Technische Universität München | The maturation of most SHRs strictly depends on the interaction with Hsp90. Co-chaperones such as Hop/Sti1 and the large peptidylprolyl isomerase (PPIase) have strong influences on the activation. | and the NLR protein may dissociate from Hsp90. (D) Hsp90-R2TP complex. Model of the R2TP complex in yeast. Pih1 interacts with Rvb1/2 | the phosphorylation states of Hsp90 must be precisely regulated in order to maintain the proper function of Hsp90. In addition | Hsp90 reaches a more compact state | provide another level of regulation. They influence the conformational cycle | in which first one Hop/Sti1 binds to the Hsp90 dimer and stabilizes its open conformation. As a result | 59 | was also reduced consistent with the notion thatHsp90 acts as an NO sensor. This provides a feedback mechanism to inhibit further eNOS activation. Nitrosylation or mutation of the modified C-terminal cysteine residue in Hsp90 led to an ATPase-incompetent state in which the N-terminal domains are kept in the open conformation. The result indicates that nitrosylation has a profound impact on the inter-domain communication in the Hsp90 dimer. Hsp90 client protein recognition Top To date | phosphorylation also modulates the interaction with co-chaperones and thus exerts further influence on the Hsp90 machinery. For example | PDB 2CG9). The N-domain is depicted in green | Rar1 | together with Hsp90 and a PPIase. It facilitates the maturation of client proteins by stabilizing the closed conformation of Hsp90. As a result | it is indispensable for maintaining the hormone binding activity of the glucocorticoid receptor (GR) and progesterone receptor (PR). | Aha1 is the most powerful ATPase activator of Hsp90. It binds the N- and M-domains of Hsp90. | tyrosine phosphorylation on Hsp90 disrupts the interaction with Cdc37 and promotes the recruitment of Aha1. C-terminal phosphorylation of Hsp90 regulates alternate binding to co-chaperones Chip and Hop | is partially inhibited in the presence of p23/Sba1. | which facilitate the maturation of client proteins. In addition | a new model of the chaperone cycle emerges [Figure 3]A | and Hsp90 returns to the open conformation again. Figure 2: Conformational cycle of Hsp90. After fast ATP binding | c-Src kinase | and NMR-based approaches suggested that for heat-treated p53 | more than 20 co-chaperones have been identified. | we just start to understand their contributions to client protein activation. Regulation of Hsp90 by posttranslational modifications Top Posttranslational modifications are another important regulatory element of the Hsp90 machinery. Different posttranslational modifications such as phosphorylation | which is indispensable for the release of the client protein | 60 | Hsp90 and the R2TP complex are involved in the biogenesis and assembly of snoRNPs. Notably | activation | Hsp90 and Sgt1 form a ternary complex with the co-chaperone Rar1 | proposed that Hsp90-bound p53 is in a molten globule state. In contrast | while bacteria possess an Hsp90 protein | Buchner J. Structure | such as phosphorylation and acetylation | and methylation tightly control the function of Hsp90 and thus influence the maturation of client proteins. Phosphorylation Phosphorylation is the most frequently detected posttranslational modification of Hsp90. A number of different tyrosine or serine phosphorylation sites have been identified and investigated for their impact on Hsp90's chaperone function. For example | the so-called Gyrase | which determine cellular protein folding/degradation balances. Furthermore | as it contains crucial catalytic residues for forming the composite ATPase site. Moreover | According to reconstitution experiments | and the AAA+ ATPase Rvb1 and Rvb2) has been extensively investigated [Figure 3]D. | general flexibility | In yeast | Department of Chemistry | strongly influences the binding between Hsp90 and its client protein. In general | intracellular transport | Function and Regulation of the Hsp90 Machinery. Biomed J [serial online] 2013 [cited 2014 Dec 31];36:106-17. Available from: http://www.biomedj.org/text.asp?2013/36/3/106/113230 Heat shock protein 90 (Hsp90) | a middle domain (M-domain) | Another aspect which supports the idea that Hsp90 may be involved in the ubiquitin-proteasome pathway is the discovery of a protein called carboxyl terminus of Hsp70-interacting protein (CHIP). As an E3 ubiquitin ligase | and the C-domain of Tah1. Tah1 binds to the C-terminal MEEVD motif of Hsp90 through its TPR domain. Click here to view Hop/Sti1 serves as an adaptor protein between Hsp70 and Hsp90 and facilitates the transfer of client protein. | Hsc82 and Hsp82 | belong to this group. The TPR-containing PPIases contain a PPIase domain | It was originally identified in Saccharomyces cerevisiae as a gene essential for cell cycle progression. | leading to an asymmetric Hsp90 intermediate complex. After the binding of ATP and p23/Sba1 | v-Src is an aggregation-prone protein and much more sensitive to thermal and heat denaturation than c-Src. In the case of p53 | the function of PPIases in SHR complexes is not well understood. They may be selected by specific client proteins. For example | analytical ultracentrifugation (aUC) | the Hsp90 ATPase activity is inhibited. The other TPR-acceptor site is then preferentially occupied by a PPIase | the αC-β4 loop in kinases | which consists of three TPR motifs and recognizes the C-terminal MEEVD motif in Hsp90. Besides Hop/Sti1 | and steroid hormone receptors (SHRs). | mutant CFTRΔF508 | 85747 Garching Germany Login to access the Email id Crossref citations 19 PMC citations 11 DOI: 10.4103/2319-4170.113230 PMID: 23806880 Get Permissions Abstract Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction | and Cyp40 (yeast homologues Cpr6/Cpr7) | Hagn et al. reported a native-like structure of p53 interaction with Hsp90. Further analysis seems to be required to resolve this conundrum and to determine the molecular mechanism for client recognition. Hsp90 and protein degradation Top Although in general | PDB 2IOQ) and nucleotide-bound yeast Hsp90 in the closed conformation (right | In the apo state | Hsp90 reaches a fully closed state in which ATP hydrolysis occurs. After ATP is hydrolyzed | and inter-domain communication. | an N-terminal ATP-binding domain (N-domain) | bacterial Hsp90 is not essential and its precise function remains to be investigated. Recent studies suggest that it collaborates with the DnaK (Hsp70) system in substrate remodeling and may function against oxidative stress. | nitrosylation | have been discovered in recent years. | neither Hsp90 nor R2TP are components of the mature snoRNP complex. The R2TP-Hsp90 complex works together with a prefoldin-like complex in RNA polymerase II assembly. This complex interacts with unassembled Rpb1 and promotes its cytoplasmic assembly and translocation to the nucleus. In addition to the activation of client protein | 85 | CK2 protein kinase | 89 | the opening of the C-domains is anti-correlated to the closing of the N-domain. A conserved MEEVD motif at the C-terminal end serves as the docking site for the interaction with co-chaperones which contain a tetratricopeptide repeat (TPR) clamp. Figure 1: Open and closed conformation of Hsp90. Crystal structures of full-length Hsp90 from E. coli (HtpG) in the open conformation (left | release ADP as well as inorganic phosphate (Pi) | a third complex that contains a PPIase and the co-chaperone p23 had been found as the last step of the cycle. | This small acidic protein contains an unstructured C-terminal tail | Hsp90 binds the largely unfolded protein. Park et al | Histindine Kinase | which seem to be in a dynamic equilibrium [Figure 1]. | Structural studies revealed that Hsp90 spontaneously adopts structurally distinct conformations | Sgt1 has no inherent Hsp90 ATPase regulatory activity due to differences in interaction. Interestingly | many others related to | nuclear migration (NudC) | Munich | like Fkbp52 | Hsp90 adopts the "closed" conformation which weakens the binding of Hop/Sti1 and therefore promotes its exit. Another PPIase or TPR co-chaperone can potentially bind to form the final complex together with Hsp90 and p23/Sba1. Following ATP hydrolysis | biochemical experiments suggest that p53 interacts with Hsp90 in a rather folded state. | the activity of Hsp90-specific clients is significantly reduced | Hsp70 and Hsp40 interact with newly synthesized kinases. Protein kinases are recruited to Hsp90 though the action of Hop/Sti1 and the kinase-specific co-chaperone Cdc37. Both are able to stabilize the Hsp90/kinase complex. Protein phosphatase Pp5 and the ATPase activator Aha1 release Hop/Sti1 from Hsp90. At a later stage | with the M-domain of Hsp90 | co-chaperones are also involved in other physiological processes | Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function | the interaction of Cdc37 with Hsp90 leads to the stabilization of the open conformation and the inhibition of Hsp90 ATPase activity. In contrast to the co-chaperones discussed above | it is not involved in the interaction with Hsp90. Functionally | the protein phosphatase Ppt1 deletion compromised the activation of specific clients. Therefore | and a client protein form an "early complex." The client protein is transferred from Hsp70 to Hsp90 through the adaptor protein Hop/Sti1. One Hop/Sti1 bound is sufficient to stabilize the open conformation of Hsp90. The other TPR-acceptor site is preferentially occupied by a PPIase | Recent biophysical studies using ensemble and single molecule fluorescence resonance energy transfer (FRET) assays allowed to further dissect the ATP-induced conformational changes [Figure 2]. | CHIP can ubiquitinate unfolded proteins. It also interacts with the C-terminus of Hsp70 and Hsp90 through its TPR domain. | the R2TP complex (consisting of Tah1 | and a C-terminal dimerization domain (C-domain) [Figure 1]. Except for the charged linker located between the N- and M-domains in eukaryotic Hsp90 | such as formation of the active sites | several reports have shown that Hsp90 is also required for the degradation of ER membrane proteins such as cytochrome p450 2E1 | Deacetylation of Hsp90 drives the formation of Hsp90 client complexes and promotes the maturation of the client protein GR. Hsp90 can be acetylated at different sites. A study from Necker's lab pointed out that K294 | evolutionarily conserved split ATPases | Sgt1 interacts with Hsp90 as well as with an NLR protein. In the stable ternary complex | and inter-domain communications. In this review | we discuss the recent progress made in understanding the Hsp90 machinery. Keywords: ATPase | an acetylation site in the M-domain | which suggests a noncatalytic role of PPIases in the regulation of SHR signaling. In contrast to Hop/Sti1 and the TPR-PPIases | Sgt1 is promoted to interact with Hsp90 as well as with an NLR protein. In the stable ternary complex | The co-chaperone Tah1 interacts with Hsp90 through its TPR domain and its C-terminal region binds Pih1 | and electron microscopy] provided insight into how the exchange of co-chaperones is regulated. | A number of different kinases can phosphorylate Hsp90 | the N-terminal dimerization leads to the formation of the second intermediate state (I2) | it was also found to facilitate protein degradation. In addition to soluble cytosolic proteins | which leads to the final activation of protein kinases. Cdc37 is specific for chaperoning kinases. | and thus | The presence of Aha1 enables Hsp90 to bypass the I1 state and to directly reach I2 in the ATPase cycle. The activation of specific clients such as viral Src kinase (v-Src) and SHRs is severely affected in Aha1 knockout cells. Moreover | of which Hsp82 is up-regulated up to 20 times under heat stress. Hsp90α and Hsp90β are the two major isoforms in the cytoplasm of mammalian cells. Hsp90α is inducible under stress conditions | Hsp70 and Hsp40 interact with newly synthesized kinases. Protein kinases are recruited to Hsp90 through the action of Hop/Sti1 and the kinase-specific co-chaperone Cdc37. Both are able to stabilize the Hsp90/kinase complex. At a later stage | Aha1 can release Cdc37 from Hsp90 together with nucleotides. (C) Hsp90 chaperone cycle for NLRs. Rar1 binds to the N-domain of Hsp90 through its Chord1 domain and prevents the formation of the closed conformation. This interaction supports the binding of Rar1-Chord2 to the N-domain in the other protomer. With the association of Rar1-Chord2 | this domain organization is conserved from bacteria to man. Hsp90 is a member of a special class of structurally related | which is structurally similar to p23/Sba1. | called HtpG in Escherichia More Details coli | and members of the PPIase family | Mammalian Hsp90 is a target of S-nitrosylation mediated by NO produced by its client protein | Cyp40 is most abundant in estrogen receptor (ER) complexes and Fkbp52 mediates potentiation of GR through increasing GR hormone-binding affinity. Interestingly | there are two Hsp90 isoforms in the cytosol | no Hsp90 gene has been found in archea. | Johannes Buchner2 1 Division of Biology | the central player in this process | different co-chaperones work together to facilitate the maturation of Hsp90 clients. The composition of co-chaperone complexes seems to depend to some degree on the presence of a specific client protein. The chaperone cycle for SHRs Early work on Hsp90 mainly focused on the co-chaperone requirement for the activation of SHRs. | These results suggest that there may be a dynamic equilibrium between the different conformations of Hsp90 and this conformational plasticity is functionally important since it may allow Hsp90 to adapt to different client proteins. Co-chaperone regulation of Hsp90 Top Co-chaperone regulation is a conserved feature of the eukaryotic Hsp90 system. To date | which catalyzes the interconversion of the cis-trans isomerization of peptide bonds prior to proline residues and a TPR domain for the interaction with Hsp90. Most of these large PPIases show independent chaperone activity. | nuclear magnetic resonance (NMR) spectroscopy | Hsp90 does not only function in protein folding but also contribute to various cellular processes including signal transduction | which contain a Bergerat ATP-binding fold. Another interesting feature of the ATP binding region is that several conserved amino acid residues form a "lid" that closes over the nucleotide binding pocket in the ATP-bound state but is open during the ADP-bound state. The M-domain of Hsp90 is involved in ATP hydrolysis | California Institute of Technology | USA 2 Center for Integrated Protein Science | and apolipoprotein B. | innate immunity | and melanoma progression (TTC4). The above examples provide a glimpse on Hsp90 co-chaperone cycles. For some cycles | Sgt1 | Hsp90 slowly reaches the first intermediate state (I1) | is essential in eukaryotic cells. | this is not the only determinant for the interaction as other regions adjacent to the kinase domain also influence the binding to Hsp90. | Rar1 binds to the N-domain of Hsp90 through its Chord1 domain and prevents the formation of the closed conformation [Figure 3]C. This interaction supports the binding of Rar1-Chord2 to the N-domain in the other protomer. With the association of Rar1-Chord2 | Aha1 plays a critical role in the inherited misfolding disease cystic fibrosis (CF) through participating in the quality control pathway of the cystic fibrosis transmembrane conductance regulator (CFTR). Down-regulation of Aha1 could rescue the phenotype caused by misfolded CFTR. Recent research highlighted the function of Aha1 in the progression of the Hsp90 cycle. It efficiently displaces Hop/Sti1 from Hsp90 and promotes the transition from the open to closed conformation together with a PPIase in a synergistic manner. Pp5/Ppt1 is a protein phosphatase which is involved in this cycle through regulating the phosphorylation states of Cdc37. It associates with Hsp90 through its N-terminal TPR domain. Binding to Hsp90 results in the abrogation of the intrinsic inhibition of Pp5/Ppt1. Pp5/Ppt1 specifically dephosphorylates Hsp90 and Cdc37 in Hsp90 complexes. | for example | However | and Swe1Wee1 kinase. | in which the M-domain repositions and interacts with the N-domain. Then Hsp90 reaches a fully closed state in which ATP hydrolysis occurs. After ATP is hydrolyzed | Hop/Sti1 is a member of the large group of TPR co-chaperones. They contain a specialized conserved TPR-clamp domain | SHRs must pass through three complexes with different co-chaperone compositions chronologically to reach their active conformation. Hsp70/Hsp40 were identified as components in the "early complex." After association with Hsp90 through the adaptor protein Hop | and RNA modification | it became an interesting target for cancer therapy. Structurally | acetylation weakens Hsp90-client interaction | In addition to the intermediate complex | protein kinase A (PKA) | p300 was reported to be the acetyltransferase and HDAC6 acts as a deacetylase which removes the acetyl group from the protein. | Trap-1 in the mitochondrial matrix | some fundamental questions related to client proteins still remained unanswered | thus permitting access by a catalytic arginine residue of the M-domain to the ATP binding site and promoting ATP hydrolysis. Once ATP is hydrolyzed | an unstable non-TPR co-chaperone of Hsp90 [Figure 3]D. During the maturation of snoRNP | release ADP and Pi | many of them are at the same time Hsp90 client proteins. This indicates that the change of phosphorylation states of Hsp90 may influence the folding and activation of certain groups of client proteins. Acetylation Acetylation is a reversible modification mediated by opposing actions of acetyltransferases and deacetylases. Hsp90 acetylation and its influence on the chaperone machinery have been extensively investigated in recent years. In the case of Hsp90 | Hsp40 | Pasadena | and the folded client are released from Hsp90. Figure 3: Hsp90 chaperone cycles. (A) Hsp90 chaperone cycle for SHRs. Hsp70 | such as the location of the client-binding sites on Hsp90. Current evidence suggests that binding sites could be localized in each of the domains of Hsp90. Another intriguing question unsolved so far is how Hsp90 recognizes its clients. Hsp90 clients belong to different families and do not share common sequences or structural motifs. Although some regions were identified which are important for the recognition of certain group of clients | The CHIP knockdown is known to stabilize some Hsp90 clients | the ATPase activator Aha1 can release Cdc37 from Hsp90 | which is essential for its intrinsic chaperone activity. | The interaction with the Hsp90 machinery enables their correct folding | and Hsp90 returns to the open conformation. Click here to view Notably | The chaperone cycle is not completely understood yet. However | Hsp90 fails to support the activation of the client protein. Nitrosylation S-nitrosylation is a reversible covalent modification of reactive cysteine thiols in proteins by nitric oxide (NO). | Cdc37 interacts with kinases through its N-terminal domain and binds to the N-domain of Hsp90 via its C-terminal part. Similar to Hop/Sti1 | Based on these results | in which the M-domain repositions and interacts with the N-domain. Then | termed "open conformation" [Figure 1]. ATP binding triggers a series of conformational changes including repositioning of the N-terminal lid region and a dramatic change in the N-M domain orientation. Finally | endothelial nitric oxide synthase (eNOS). S-nitrosylation was reported as a negative regulator which inhibits the ATPase activity of Hsp90. In addition | p23 was identified as a component in SHR complexes | transport | we have obtained a full picture with detailed information; for others | and even degradation. | the N-domains dissociate | only phosphorylated Hsp90 stimulates the activity of the Hsp90 client protein heme-regulated inhibitor kinase (HRI); dephosphorylation eliminated the ability of Hsp90 to activate this client protein. Interestingly | the ATP hydrolysis | Hsp90 is not required for de novo folding of most proteins but facilitates the final maturation of a selected clientele of proteins. Hsp90 clients include protein kinases | the Hsp90-Tah1 complex stabilizes Pih1 in vivo and prevents its aggregation in vitro. The Tah1-Pih1 heterodimer is able to inhibit the ATPase activity of Hsp90. Tah1 and Pih1 are then transferred to the Rvb1/2 complex leading to the formation of the R2TP complex [Figure 3]D. Together | 101 | 102 | Function and Regulation of the Hsp90 Machinery Jing Li1 | termed "closed conformation" in which the N-domains are dimerized [Figure 1]. | together with nucleotides | the "intermediate complex" is formed. | p23/Sba1 and the folded client are released from Hsp90. (B) Hsp90 chaperone cycle for kinases. In the early stage | transcription factors such as p53
Journal Article
Journal of Molecular Biology, ISSN 0022-2836, 07/2019, Volume 431, Issue 15, pp. 2729 - 2746
Members of the Hsp90 and Hsp70 families of molecular chaperones are imp\ortant for the maintenance of protein homeostasis and cellular recovery following... 
HtpG | Hsp82 | DnaJ | Hsp40 | Ssa1 | MOLECULAR CHAPERONE HSP90 | HTPG | DOMAIN | CLIENT-BINDING | DNAJ | CHARGED LINKER | CRYSTAL-STRUCTURE | BIOCHEMISTRY & MOLECULAR BIOLOGY | ESCHERICHIA-COLI HSP90 | HEAT-SHOCK-PROTEIN | REVEALS | Heat shock proteins | Bacteria | Crosslinked polymers | Escherichia coli | Protein binding
Journal Article
PLoS ONE, ISSN 1932-6203, 05/2016, Volume 11, Issue 5, p. e0155583
Sepsis is a systemic inflammatory disorder, accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated... 
GELDANAMYCIN ANALOG | HEAT-SHOCK-PROTEIN-70 | OXIDATIVE STRESS | ACTIVATION | INFLAMMATORY RESPONSES | SHOCK-PROTEIN 90 | MULTIDISCIPLINARY SCIENCES | DISSEMINATED INTRAVASCULAR COAGULATION | HEME OXYGENASE-1 | SEPSIS | EXPRESSION | Multiple Organ Failure - metabolism | Rats, Wistar | Multiple Organ Failure - chemically induced | Tumor Necrosis Factor-alpha - blood | Caspase 3 - metabolism | Endotoxemia - chemically induced | Male | Alanine Transaminase - blood | Endotoxemia - pathology | Interleukin-6 - blood | HSP70 Heat-Shock Proteins - biosynthesis | Multiple Organ Failure - pathology | Nitric Oxide - blood | Lipopolysaccharides - toxicity | Creatine Kinase - blood | Endotoxemia - drug therapy | Rats | Lactams, Macrocyclic - pharmacology | Benzoquinones - pharmacology | Animals | Transcription Factor RelA - metabolism | HSP90 Heat-Shock Proteins - antagonists & inhibitors | L-Lactate Dehydrogenase - blood | Creatinine - blood | Endotoxemia - metabolism | Multiple Organ Failure - drug therapy | Complications and side effects | Prognosis | Multiple organ failure | Heat shock proteins | Physiological aspects | Sepsis | Development and progression | Genetic aspects | Research | Risk factors | Creatine kinase | Creatine | Caspase-3 | Lipopolysaccharides | Antioxidants | Ischemia | Animal tissues | Life sciences | Endotoxemia | NF-κB protein | Cytokines | Hsp70 protein | Gene expression | Survival | Nitric-oxide synthase | Inhibitors | Nitric oxide | Oxidative stress | Hsp90 protein | Disseminated intravascular coagulation | Activation | Kinases | Interleukin 6 | Metabolites | E coli | Rodents | Atherosclerosis | Heme | Bacteria | Pretreatment | Creatinine | Alanine | Bacterial infections | Multiple organ dysfunction syndrome | Neutrophils | Organs | Caspase | Lactate dehydrogenase | Inflammation | Pharmacology | Hypotension | L-Lactate dehydrogenase | Prothrombin | Alanine transaminase | Lactic acid | Laboratory animals | Prolongation | Heat shock | Veins & arteries
Journal Article
Current Medicinal Chemistry, ISSN 0929-8673, 11/2008, Volume 15, Issue 26, pp. 2702 - 2717
Journal Article
Cell Stress & Chaperones, ISSN 1355-8145, 3/2011, Volume 16, Issue 2, pp. 203 - 218
Heat shock protein 90 (HSP90) is a conserved molecular chaperone that functions as part of complexes in which different client proteins target it to diverse... 
Biological taxonomies | Dehydrogenases | Gels | Ribosomal proteins | Antibodies | Bacteria | Shewanella | Viability | Psychrophilic bacteria | Cell extracts | Biochemistry, general | HSP90 | HTPG | Protein interactions | Biomedicine general | Psychrophiles | Cell Biology | Biomedicine | Immunology | High temperature protein G | Extremophiles | Cancer Research | Cold adaptation | Heat shock protein 90 | THERMAL-STRESS MANAGEMENT | GROEL | ESCHERICHIA-COLI | CHAPERONE | LOW-TEMPERATURE | CELL BIOLOGY | CYANOBACTERIA | ADAPTATION | HEAT-SHOCK GENE | EXPRESSION | Cold Temperature | Gammaproteobacteria - metabolism | Electrophoresis, Gel, Two-Dimensional | Gammaproteobacteria - physiology | Gammaproteobacteria - classification | Microbial Viability | Phylogeny | Multiprotein Complexes - physiology | Heat-Shock Response | Multiprotein Complexes - chemistry | HSP90 Heat-Shock Proteins - chemistry | HSP90 Heat-Shock Proteins - metabolism | Protein Binding | Environment | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | Proteins | Heat shock proteins | Ionization | Mass spectrometry | Analysis | Adaptations | Cell culture | Hsp90 protein | Energy metabolism | Translation | Gel electrophoresis | Mass spectroscopy | Malate dehydrogenase | Alcohol dehydrogenase | Chaperones | Isocitrate lyase | Lasers | DnaK protein | succinyl-CoA | Original Paper
Journal Article
MBIO, ISSN 2150-7511, 05/2019, Volume 10, Issue 3, p. e00269-19
Protein synthesis, folding, and degradation are an accurately regulated process occurring in every organism and called proteostasis. This process is essential... 
HTPG | protein chaperone | proteases | stress adaptation | heat shock | MICROBIOLOGY | protein folding | proteostasis | STRESS | Life Sciences | Biochemistry, Molecular Biology
Journal Article
Scientific Reports, ISSN 2045-2322, 12/2018, Volume 8, Issue 1, pp. 14198 - 10
Surface adhesins of pathogens and probiotics strains are implicated in mediating the binding of microbes to host. Mucus-binding protein (Mub) is unique to gut... 
Hsp90 protein | Lactic acid bacteria | Adhesins | Mucosa | Mucus | Plant cells | Proteins | Microspheres | Laminin | E coli | Intestine | Calcium-binding protein | Digestive tract | Sodium tripolyphosphate | Pathogens | Digestive system | Feasibility studies | Tripolyphosphate | C-Terminus | Host-pathogen interactions | Probiotics | Enterocytes | Sodium | Cell lines | Ligands | Lactic acid | Chitosan
Journal Article
PLoS ONE, ISSN 1932-6203, 2011, Volume 6, Issue 6, p. e21231
Background: The molecular chaperone heat shock protein 90 (Hsp90) plays an important role in folding stabilization and activation of client proteins. Besides,... 
LEISHMANIA-INFANTUM | HEAT-SHOCK PROTEINS | IN-VITRO | HSP70 | DENDRITIC CELLS | MULTIDISCIPLINARY SCIENCES | TOLL-LIKE RECEPTORS | INNATE | TOXOPLASMA-GONDII | HSP83 | LYMPHOCYTES | Recombinant Proteins - metabolism | B-Lymphocytes - cytology | Plant Proteins - pharmacology | Tobacco - metabolism | Electrophoresis, Polyacrylamide Gel | Cells, Cultured | Recombinant Proteins - genetics | Recombinant Proteins - pharmacology | HSP90 Heat-Shock Proteins - pharmacology | Blotting, Western | B-Lymphocytes - drug effects | Plant Proteins - genetics | Animals | Flow Cytometry | Tobacco - genetics | HSP90 Heat-Shock Proteins - metabolism | Female | Cell Proliferation - drug effects | HSP90 Heat-Shock Proteins - genetics | Mice | Mice, Inbred BALB C | Plant Proteins - metabolism | B-Lymphocytes - metabolism | Fluorescent Antibody Technique, Indirect | Arabidopsis thaliana | Gene mutations | Analysis | Heat shock proteins | B cells | T cells | Recombinant proteins | Mitogens | Cell proliferation | Hsp90 protein | Amino acids | Lymphocytes T | Biochemistry | Kinases | Lipopolysaccharides | Proteins | Immunology | E coli | Affinity chromatography | Lymphocytes | Protein folding | Rodents | Toll-like receptors | Bacteria | Trends | Recombinant | Immune system | Spleen | Pathogens | Antigens | Immunostimulation | Polypeptides | CD19 antigen | Incubation | Dendritic cells | TLR4 protein | Plants | Overexpression | Lymphocytes B | Isoforms | Point mutation | Scientific imaging | Mutation | Immunofluorescence | In vitro methods and tests | Mass spectrometry | Binding sites | Heat shock | Apoptosis
Journal Article