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Chaperone PDB id
1ah6
Jmol
Contents
Protein chain
213 a.a. *
Waters ×310
* Residue conservation analysis
PDB id:
1ah6
Name: Chaperone
Title: Structure of the tetragonal form of the n-terminal domain of the yeast hsp90 chaperone
Structure: Heat shock protein 90. Chain: a. Fragment: n-terminal domain. Synonym: hsp90
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.206     R-free:   0.255
Authors: C.Prodromou,S.M.Roe,L.H.Pearl
Key ref: C.Prodromou et al. (1997). A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone. Nat Struct Biol, 4, 477-482. PubMed id: 9187656 DOI: 10.1038/nsb0697-477
Date:
14-Apr-97     Release date:   22-Oct-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P02829  (HSP82_YEAST) -  ATP-dependent molecular chaperone HSP82
Seq:
Struc: 		 
Seq:
Struc: 		709 a.a.
213 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to stress   2 terms 
  Biochemical function     unfolded protein binding     2 terms  

 

 
DOI no: 10.1038/nsb0697-477 Nat Struct Biol 4:477-482 (1997)
PubMed id: 9187656  
 
 
A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone.
C.Prodromou, S.M.Roe, P.W.Piper, L.H.Pearl.
 
  ABSTRACT  
 
Hsp90 is a highly specific chaperone for many signal transduction proteins, including steroid hormone receptors and a broad range of protein kinases. The crystal structure of the N-terminal domain of the yeast Hsp90 reveals a dimeric structure based on a highly twisted sixteen stranded beta-sheet, whose topology suggests a possible 30-domain-swapped structure for the intact Hsp90 dimer. The opposing faces of the beta-sheets in the dimer define a potential peptide-binding cleft, suggesting that the N-domain may serve as a molecular 'clamp' in the binding of ligand proteins to Hsp90.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21414251 K.A.Krukenberg, T.O.Street, L.A.Lavery, and D.A.Agard (2011).
Conformational dynamics of the molecular chaperone Hsp90.
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20531426 M.Taipale, D.F.Jarosz, and S.Lindquist (2010).
HSP90 at the hub of protein homeostasis: emerging mechanistic insights.
  Nat Rev Mol Cell Biol, 11, 515-528.  
19165152 C.Graf, M.Stankiewicz, G.Kramer, and M.P.Mayer (2009).
Spatially and kinetically resolved changes in the conformational dynamics of the Hsp90 chaperone machine.
  EMBO J, 28, 602-613.  
19032597 C.K.Vaughan, P.W.Piper, L.H.Pearl, and C.Prodromou (2009).
A common conformationally coupled ATPase mechanism for yeast and human cytoplasmic HSP90s.
  FEBS J, 276, 199-209.  
18668349 F.Li, W.Luan, C.Zhang, J.Zhang, B.Wang, Y.Xie, S.Li, and J.Xiang (2009).
Cloning of cytoplasmic heat shock protein 90 (FcHSP90) from Fenneropenaeus chinensis and its expression response to heat shock and hypoxia.
  Cell Stress Chaperones, 14, 161-172.  
19300478 G.Morra, G.Verkhivker, and G.Colombo (2009).
Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer.
  PLoS Comput Biol, 5, e1000323.  
19685544 M.Sgobba, and G.Rastelli (2009).
Structure-based and in silico design of Hsp90 inhibitors.
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19200020 M.W.Amolins, and B.S.Blagg (2009).
Natural product inhibitors of Hsp90: potential leads for drug discovery.
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19361515 R.M.Immormino, L.E.Metzger, P.N.Reardon, D.E.Dollins, B.S.Blagg, and D.T.Gewirth (2009).
Different poses for ligand and chaperone in inhibitor-bound Hsp90 and GRP94: implications for paralog-specific drug design.
  J Mol Biol, 388, 1033-1042.
PDB codes: 2exl 2fxs 2gfd
18826913 A.Yan, G.H.Grant, and W.G.Richards (2008).
Dynamics of conserved waters in human Hsp90: implications for drug design.
  J R Soc Interface, 5, S199-S205.  
18511558 G.Colombo, G.Morra, M.Meli, and G.Verkhivker (2008).
Understanding ligand-based modulation of the Hsp90 molecular chaperone dynamics at atomic resolution.
  Proc Natl Acad Sci U S A, 105, 7976-7981.  
18647240 N.D.Thomsen, and J.M.Berger (2008).
Structural frameworks for considering microbial protein- and nucleic acid-dependent motor ATPases.
  Mol Microbiol, 69, 1071-1090.  
17936703 D.E.Dollins, J.J.Warren, R.M.Immormino, and D.T.Gewirth (2007).
Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones.
  Mol Cell, 28, 41-56.
PDB codes: 2o1t 2o1u 2o1v 2o1w
17826744 M.A.Brown, L.Zhu, C.Schmidt, and P.W.Tucker (2007).
Hsp90--from signal transduction to cell transformation.
  Biochem Biophys Res Commun, 363, 241-246.  
17908693 N.Wayne, and D.N.Bolon (2007).
Dimerization of Hsp90 is required for in vivo function. Design and analysis of monomers and dimers.
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16731965 F.Chu, J.C.Maynard, G.Chiosis, C.V.Nicchitta, and A.L.Burlingame (2006).
Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94.
  Protein Sci, 15, 1260-1269.  
16461354 K.Richter, S.Moser, F.Hagn, R.Friedrich, O.Hainzl, M.Heller, S.Schlee, H.Kessler, J.Reinstein, and J.Buchner (2006).
Intrinsic inhibition of the Hsp90 ATPase activity.
  J Biol Chem, 281, 11301-11311.
PDB code: 2akp
16756493 L.H.Pearl, and C.Prodromou (2006).
Structure and mechanism of the Hsp90 molecular chaperone machinery.
  Annu Rev Biochem, 75, 271-294.  
17201776 M.A.Theodoraki, and A.C.Mintzas (2006).
cDNA cloning, heat shock regulation and developmental expression of the hsp83 gene in the Mediterranean fruit fly Ceratitis capitata.
  Insect Mol Biol, 15, 839-852.  
16556029 C.Dai, and L.Whitesell (2005).
HSP90: a rising star on the horizon of anticancer targets.
  Future Oncol, 1, 529-540.  
16333984 J.Kishimoto, Y.Fukuma, A.Mizuno, and T.K.Nemoto (2005).
Identification of the pentapeptide constituting a dominant epitope common to all eukaryotic heat shock protein 90 molecular chaperones.
  Cell Stress Chaperones, 10, 296-311.  
15939019 K.D.Corbett, and J.M.Berger (2005).
Structural dissection of ATP turnover in the prototypical GHL ATPase TopoVI.
  Structure, 13, 873-882.
PDB codes: 1z59 1z5a 1z5b 1z5c
15837196 Q.Huai, H.Wang, Y.Liu, H.Y.Kim, D.Toft, and H.Ke (2005).
Structures of the N-terminal and middle domains of E. coli Hsp90 and conformation changes upon ADP binding.
  Structure, 13, 579-590.
PDB codes: 1y4s 1y4u
15766533 R.Zhao, M.Davey, Y.C.Hsu, P.Kaplanek, A.Tong, A.B.Parsons, N.Krogan, G.Cagney, D.Mai, J.Greenblatt, C.Boone, A.Emili, and W.A.Houry (2005).
Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone.
  Cell, 120, 715-727.  
16333321 R.Zhao, and W.A.Houry (2005).
Hsp90: a chaperone for protein folding and gene regulation.
  Biochem Cell Biol, 83, 703-710.  
15302866 D.K.Marsee, A.Venkateswaran, H.Tao, D.Vadysirisack, Z.Zhang, D.D.Vandre, and S.M.Jhiang (2004).
Inhibition of heat shock protein 90, a novel RET/PTC1-associated protein, increases radioiodide accumulation in thyroid cells.
  J Biol Chem, 279, 43990-43997.  
15466438 G.Siligardi, B.Hu, B.Panaretou, P.W.Piper, L.H.Pearl, and C.Prodromou (2004).
Co-chaperone regulation of conformational switching in the Hsp90 ATPase cycle.
  J Biol Chem, 279, 51989-51998.  
15139806 K.D.Corbett, and J.M.Berger (2004).
Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases.
  Annu Rev Biophys Biomol Struct, 33, 95.  
15292259 R.M.Immormino, D.E.Dollins, P.L.Shaffer, K.L.Soldano, M.A.Walker, and D.T.Gewirth (2004).
Ligand-induced conformational shift in the N-terminal domain of GRP94, an Hsp90 chaperone.
  J Biol Chem, 279, 46162-46171.
PDB codes: 1tbw 1tc0 1tc6
14754890 T.Gidalevitz, C.Biswas, H.Ding, D.Schneidman-Duhovny, H.J.Wolfson, F.Stevens, S.Radford, and Y.Argon (2004).
Identification of the N-terminal peptide binding site of glucose-regulated protein 94.
  J Biol Chem, 279, 16543-16552.  
12970348 K.L.Soldano, A.Jivan, C.V.Nicchitta, and D.T.Gewirth (2003).
Structure of the N-terminal domain of GRP94. Basis for ligand specificity and regulation.
  J Biol Chem, 278, 48330-48338.
PDB codes: 1qy5 1qy8 1qye 1qyh 1u2o
12667448 P.Meyer, C.Prodromou, B.Hu, C.Vaughan, S.M.Roe, B.Panaretou, P.W.Piper, and L.H.Pearl (2003).
Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions.
  Mol Cell, 11, 647-658.
PDB code: 1hk7
14514358 R.Kumar, A.Musiyenko, and S.Barik (2003).
The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin.
  Malar J, 2, 30.  
12492485 S.Yamada, T.Ono, A.Mizuno, and T.K.Nemoto (2003).
A hydrophobic segment within the C-terminal domain is essential for both client-binding and dimer formation of the HSP90-family molecular chaperone.
  Eur J Biochem, 270, 146-154.  
12617036 Y.Miyata (2003).
[Molecular chaperone HSP90 as a novel target for cancer chemotherapy]
  Nippon Yakurigaku Zasshi, 121, 33-42.  
11805114 C.Garnier, D.Lafitte, P.O.Tsvetkov, P.Barbier, J.Leclerc-Devin, J.M.Millot, C.Briand, A.A.Makarov, M.G.Catelli, and V.Peyrot (2002).
Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-terminal domain.
  J Biol Chem, 277, 12208-12214.  
  12454061 C.Welz-Voegele, J.E.Stone, P.T.Tran, H.M.Kearney, R.M.Liskay, T.D.Petes, and S.Jinks-Robertson (2002).
Alleles of the yeast Pms1 mismatch-repair gene that differentially affect recombination- and replication-related processes.
  Genetics, 162, 1131-1145.  
  11773412 J.J.Hung, C.S.Chung, and W.Chang (2002).
Molecular chaperone Hsp90 is important for vaccinia virus growth in cells.
  J Virol, 76, 1379-1390.  
11861608 P.Srivastava (2002).
Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses.
  Annu Rev Immunol, 20, 395-425.  
12121981 S.Matsumoto, E.Tanaka, T.K.Nemoto, T.Ono, T.Takagi, J.Imai, Y.Kimura, I.Yahara, T.Kobayakawa, T.Ayuse, K.Oi, and A.Mizuno (2002).
Interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 molecular chaperone.
  J Biol Chem, 277, 34959-34966.  
12189140 S.Vogen, T.Gidalevitz, C.Biswas, B.B.Simen, E.Stein, F.Gulmen, and Y.Argon (2002).
Radicicol-sensitive peptide binding to the N-terminal portion of GRP94.
  J Biol Chem, 277, 40742-40750.  
12491239 S.Walter, and J.Buchner (2002).
Molecular chaperones--cellular machines for protein folding.
  Angew Chem Int Ed Engl, 41, 1098-1113.  
11298759 C.Garnier, D.Lafitte, T.J.Jorgensen, O.N.Jensen, C.Briand, and V.Peyrot (2001).
Phosphorylation and oligomerization states of native pig brain HSP90 studied by mass spectrometry.
  Eur J Biochem, 268, 2402-2407.  
11606188 E.Tanaka, T.K.Nemoto, and T.Ono (2001).
Liberation of the intramolecular interaction as the mechanism of heat-induced activation of HSP90 molecular chaperone.
  Eur J Biochem, 268, 5270-5277.  
11584270 F.Randow, and B.Seed (2001).
Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability.
  Nat Cell Biol, 3, 891-896.  
11306353 G.Chiosis, M.N.Timaul, B.Lucas, P.N.Munster, F.F.Zheng, L.Sepp-Lorenzino, and N.Rosen (2001).
A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells.
  Chem Biol, 8, 289-299.  
  11795466 L.Bouhouche-Chatelier, A.Chadli, and M.G.Catelli (2001).
The N-terminal adenosine triphosphate binding domain of Hsp90 is necessary and sufficient for interaction with estrogen receptor.
  Cell Stress Chaperones, 6, 297-305.  
11298772 M.Minami, M.Nakamura, Y.Emori, and Y.Minami (2001).
Both the N- and C-terminal chaperone sites of Hsp90 participate in protein refolding.
  Eur J Biochem, 268, 2520-2524.  
11481425 P.T.Tran, J.A.Simon, and R.M.Liskay (2001).
Interactions of Exo1p with components of MutLalpha in Saccharomyces cerevisiae.
  Proc Natl Acad Sci U S A, 98, 9760-9765.  
11606187 T.K.Nemoto, T.Ono, T.Kobayakawa, E.Tanaka, T.T.Baba, K.Tanaka, T.Takagi, and T.Gotoh (2001).
Domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90 molecular chaperone.
  Eur J Biochem, 268, 5258-5269.  
10944121 C.Prodromou, B.Panaretou, S.Chohan, G.Siligardi, R.O'Brien, J.E.Ladbury, S.M.Roe, P.W.Piper, and L.H.Pearl (2000).
The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains.
  EMBO J, 19, 4383-4392.  
10702272 D.S.Cissel, and M.A.Beaven (2000).
Disruption of Raf-1/heat shock protein 90 complex and Raf signaling by dexamethasone in mast cells.
  J Biol Chem, 275, 7066-7070.  
10679459 L.H.Pearl, and C.Prodromou (2000).
Structure and in vivo function of Hsp90.
  Curr Opin Struct Biol, 10, 46-51.  
  10745003 M.E.Gottesman, and W.A.Hendrickson (2000).
Protein folding and unfolding by Escherichia coli chaperones and chaperonins.
  Curr Opin Microbiol, 3, 197-202.  
10938116 P.T.Tran, and R.M.Liskay (2000).
Functional studies on the candidate ATPase domains of Saccharomyces cerevisiae MutLalpha.
  Mol Cell Biol, 20, 6390-6398.  
  11189450 S.Basu, and P.K.Srivastava (2000).
Heat shock proteins: the fountainhead of innate and adaptive immune responses.
  Cell Stress Chaperones, 5, 443-451.  
10370241 A.J.Caplan (1999).
Hsp90's secrets unfold: new insights from structural and functional studies.
  Trends Cell Biol, 9, 262-268.  
9927435 C.Prodromou, G.Siligardi, R.O'Brien, D.N.Woolfson, L.Regan, B.Panaretou, J.E.Ladbury, P.W.Piper, and L.H.Pearl (1999).
Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones.
  EMBO J, 18, 754-762.  
9990037 D.F.Nathan, M.H.Vos, and S.Lindquist (1999).
Identification of SSF1, CNS1, and HCH1 as multicopy suppressors of a Saccharomyces cerevisiae Hsp90 loss-of-function mutation.
  Proc Natl Acad Sci U S A, 96, 1409-1414.  
10322418 J.Buchner (1999).
Hsp90 & Co. - a holding for folding.
  Trends Biochem Sci, 24, 136-141.  
11504487 L.Neckers, E.Mimnaugh, and T.W.Schulte (1999).
Hsp90 as an anti-cancer target.
  Drug Resist Updat, 2, 165-172.  
  10049923 L.Yue, T.L.Karr, D.F.Nathan, H.Swift, S.Srinivasan, and S.Lindquist (1999).
Genetic analysis of viable Hsp90 alleles reveals a critical role in Drosophila spermatogenesis.
  Genetics, 151, 1065-1079.  
  10082584 P.V.Shcherbakova, and T.A.Kunkel (1999).
Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations.
  Mol Cell Biol, 19, 3177-3183.  
9990018 T.Scheibel, H.I.Siegmund, R.Jaenicke, P.Ganz, H.Lilie, and J.Buchner (1999).
The charged region of Hsp90 modulates the function of the N-terminal domain.
  Proc Natl Acad Sci U S A, 96, 1297-1302.  
9707442 B.Panaretou, C.Prodromou, S.M.Roe, R.O'Brien, J.E.Ladbury, P.W.Piper, and L.H.Pearl (1998).
ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo.
  EMBO J, 17, 4829-4836.  
9827806 C.Ban, and W.Yang (1998).
Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis.
  Cell, 95, 541-552.
PDB code: 1bkn
9523119 C.V.Nicchitta (1998).
Biochemical, cell biological and immunological issues surrounding the endoplasmic reticulum chaperone GRP94/gp96.
  Curr Opin Immunol, 10, 103-109.  
9668605 I.Yahara, Y.Minami, and Y.Miyata (1998).
The 90-kDa stress protein, Hsp90, is a novel molecular chaperone.
  Ann N Y Acad Sci, 851, 54-60.  
9519293 J.M.Berger (1998).
Type II DNA topoisomerases.
  Curr Opin Struct Biol, 8, 26-32.  
  9749880 P.Csermely, T.Schnaider, C.Soti, Z.Prohászka, and G.Nardai (1998).
The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review.
  Pharmacol Ther, 79, 129-168.  
9655479 P.K.Srivastava, A.Menoret, S.Basu, R.J.Binder, and K.L.McQuade (1998).
Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world.
  Immunity, 8, 657-665.  
9817749 W.M.Obermann, H.Sondermann, A.A.Russo, N.P.Pavletich, and F.U.Hartl (1998).
In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis.
  J Cell Biol, 143, 901-910.
PDB code: 1byq
9230303 C.Prodromou, S.M.Roe, R.O'Brien, J.E.Ladbury, P.W.Piper, and L.H.Pearl (1997).
Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone.
  Cell, 90, 65-75.
PDB codes: 1a4h 1am1 1amw
9371781 D.F.Nathan, M.H.Vos, and S.Lindquist (1997).
In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone.
  Proc Natl Acad Sci U S A, 94, 12949-12956.  
9295332 J.P.Grenert, W.P.Sullivan, P.Fadden, T.A.Haystead, J.Clark, E.Mimnaugh, H.Krutzsch, H.J.Ochel, T.W.Schulte, E.Sausville, L.M.Neckers, and D.O.Toft (1997).
The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation.
  J Biol Chem, 272, 23843-23850.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.