PDBsum entry 2iop

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Chaperone PDB id
Protein chains
618 a.a. *
ADP ×4
* Residue conservation analysis
PDB id:
Name: Chaperone
Title: Crystal structure of full-length htpg, the escherichia coli hsp90, bound to adp
Structure: Chaperone protein htpg. Chain: a, b, c, d. Synonym: heat shock protein htpg, high temperature protein g, heat shock protein c62.5. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: htpg. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
3.55Å     R-factor:   0.317     R-free:   0.357
Authors: A.K.Shiau,S.F.Harris,D.A.Agard
Key ref:
A.K.Shiau et al. (2006). Structural Analysis of E. coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements. Cell, 127, 329-340. PubMed id: 17055434 DOI: 10.1016/j.cell.2006.09.027
10-Oct-06     Release date:   21-Nov-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A6Z3  (HTPG_ECOLI) -  Chaperone protein HtpG
624 a.a.
618 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     response to stress   5 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1016/j.cell.2006.09.027 Cell 127:329-340 (2006)
PubMed id: 17055434  
Structural Analysis of E. coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements.
A.K.Shiau, S.F.Harris, D.R.Southworth, D.A.Agard.
In eukaryotes, the ubiquitous and abundant members of the 90 kilodalton heat-shock protein (hsp90) chaperone family facilitate the folding and conformational changes of a broad array of proteins important in cell signaling, proliferation, and survival. Here we describe the effects of nucleotides on the structure of full-length HtpG, the Escherichia coli hsp90 ortholog. By electron microscopy, the nucleotide-free, AMPPNP bound, and ADP bound states of HtpG adopt completely distinct conformations. Structural characterization of nucleotide-free and ADP bound HtpG was extended to higher resolution by X-ray crystallography. In the absence of nucleotide, HtpG exhibits an "open" conformation in which the three domains of each monomer present hydrophobic elements into the large cleft formed by the dimer. By contrast, ADP binding drives dramatic conformational changes that allow these hydrophobic elements to converge and shield each other from solvent, suggesting a mechanism by which nucleotides could control client protein binding and release.
  Selected figure(s)  
Figure 4.
Figure 4. ADP Binding Alters the Exposure of NTD Hydrophobic Residues
Figure 5.
Figure 5. The ADP Bound Full-Length HtpG Forms a Dimer of Dimers Stabilized by an Intimate Hydrophobic Core
  The above figures are reprinted by permission from Cell Press: Cell (2006, 127, 329-340) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21776078 F.U.Hartl, A.Bracher, and M.Hayer-Hartl (2011).
Molecular chaperones in protein folding and proteostasis.
  Nature, 475, 324-332.  
21170051 J.Li, K.Richter, and J.Buchner (2011).
Mixed Hsp90-cochaperone complexes are important for the progression of the reaction cycle.
  Nat Struct Mol Biol, 18, 61-66.  
21414251 K.A.Krukenberg, T.O.Street, L.A.Lavery, and D.A.Agard (2011).
Conformational dynamics of the molecular chaperone Hsp90.
  Q Rev Biophys, 44, 229-255.  
21460846 S.J.Park, B.N.Borin, M.A.Martinez-Yamout, and H.J.Dyson (2011).
The client protein p53 adopts a molten globule-like state in the presence of Hsp90.
  Nat Struct Mol Biol, 18, 537-541.  
21210767 S.Minagawa, Y.Kondoh, K.Sueoka, H.Osada, and H.Nakamoto (2011).
Cyclic lipopeptide antibiotics bind to the N-terminal domain of the prokaryotic Hsp90 to inhibit the chaperone activity.
  Biochem J, 435, 237-246.  
21474071 T.O.Street, L.A.Lavery, and D.A.Agard (2011).
Substrate binding drives large-scale conformational changes in the Hsp90 molecular chaperone.
  Mol Cell, 42, 96.  
20089831 A.V.Koulov, P.Lapointe, B.Lu, A.Razvi, J.Coppinger, M.Q.Dong, J.Matteson, R.Laister, C.Arrowsmith, J.R.Yates, and W.E.Balch (2010).
Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis.
  Mol Biol Cell, 21, 871-884.  
20066034 D.Seeliger, and Groot (2010).
Conformational transitions upon ligand binding: holo-structure prediction from apo conformations.
  PLoS Comput Biol, 6, e1000634.  
19875381 J.J.Gano, and J.A.Simon (2010).
A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein.
  Mol Cell Proteomics, 9, 255-270.  
20635416 K.D.Corbett, and J.M.Berger (2010).
Structure of the ATP-binding domain of Plasmodium falciparum Hsp90.
  Proteins, 78, 2738-2744.
PDB code: 3k60
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.  
20670895 M.Zhang, Y.Kadota, C.Prodromou, K.Shirasu, and L.H.Pearl (2010).
Structural basis for assembly of Hsp90-Sgt1-CHORD protein complexes: implications for chaperoning of NLR innate immunity receptors.
  Mol Cell, 39, 269-281.
PDB code: 2xcm
  19890989 T.O.Street, K.A.Krukenberg, J.Rosgen, D.W.Bolen, and D.A.Agard (2010).
Osmolyte-induced conformational changes in the Hsp90 molecular chaperone.
  Protein Sci, 19, 57-65.  
19343225 B.K.Ho, and D.A.Agard (2009).
Probing the flexibility of large conformational changes in protein structures through local perturbations.
  PLoS Comput Biol, 5, e1000343.  
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.  
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.  
19554567 K.A.Krukenberg, U.M.Böttcher, D.R.Southworth, and D.A.Agard (2009).
Grp94, the endoplasmic reticulum Hsp90, has a similar solution conformation to cytosolic Hsp90 in the absence of nucleotide.
  Protein Sci, 18, 1815-1827.  
19359180 L.Neckers, M.Mollapour, and S.Tsutsumi (2009).
The complex dance of the molecular chaperone Hsp90.
  Trends Biochem Sci, 34, 223-226.  
19259122 L.Neckers, S.Tsutsumi, and M.Mollapour (2009).
Visualizing the twists and turns of a molecular chaperone.
  Nat Struct Mol Biol, 16, 235-236.  
19234467 M.Hessling, K.Richter, and J.Buchner (2009).
Dissection of the ATP-induced conformational cycle of the molecular chaperone Hsp90.
  Nat Struct Mol Biol, 16, 287-293.  
19234469 M.Mickler, M.Hessling, C.Ratzke, J.Buchner, and T.Hugel (2009).
The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis.
  Nat Struct Mol Biol, 16, 281-286.  
19125165 M.P.Mayer, C.Prodromou, and J.Frydman (2009).
The Hsp90 mosaic: a picture emerges.
  Nat Struct Mol Biol, 16, 2-6.  
19696785 M.Retzlaff, M.Stahl, H.C.Eberl, S.Lagleder, J.Beck, H.Kessler, and J.Buchner (2009).
Hsp90 is regulated by a switch point in the C-terminal domain.
  EMBO Rep, 10, 1147-1153.  
19685544 M.Sgobba, and G.Rastelli (2009).
Structure-based and in silico design of Hsp90 inhibitors.
  ChemMedChem, 4, 1399-1409.  
19553666 O.Hainzl, M.C.Lapina, J.Buchner, and K.Richter (2009).
The charged linker region is an important regulator of Hsp90 function.
  J Biol Chem, 284, 22559-22567.  
19396626 P.A.Tsaytler, J.Krijgsveld, S.S.Goerdayal, S.Rüdiger, and M.R.Egmond (2009).
Novel Hsp90 partners discovered using complementary proteomic approaches.
  Cell Stress Chaperones, 14, 629-638.  
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
19838189 S.Tsutsumi, M.Mollapour, C.Graf, C.T.Lee, B.T.Scroggins, W.Xu, L.Haslerova, M.Hessling, A.A.Konstantinova, J.B.Trepel, B.Panaretou, J.Buchner, M.P.Mayer, C.Prodromou, and L.Neckers (2009).
Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain.
  Nat Struct Mol Biol, 16, 1141-1147.  
19179103 Y.Li, T.Zhang, S.J.Schwartz, and D.Sun (2009).
New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms, clinical perspective and more potential.
  Drug Resist Updat, 12, 17-27.  
19557328 Z.Chang (2009).
Posttranslational modulation on the biological activities of molecular chaperones.
  Sci China C Life Sci, 52, 515-520.  
18287101 A.Leskovar, H.Wegele, N.D.Werbeck, J.Buchner, and J.Reinstein (2008).
The ATPase cycle of the mitochondrial Hsp90 analog Trap1.
  J Biol Chem, 283, 11677-11688.  
18332123 C.F.Cheng, J.Fan, M.Fedesco, S.Guan, Y.Li, B.Bandyopadhyay, A.M.Bright, D.Yerushalmi, M.Liang, M.Chen, Y.P.Han, D.T.Woodley, and W.Li (2008).
Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing.
  Mol Cell Biol, 28, 3344-3358.  
18492664 C.N.Cunningham, K.A.Krukenberg, and D.A.Agard (2008).
Intra- and intermonomer interactions are required to synergistically facilitate ATP hydrolysis in Hsp90.
  J Biol Chem, 283, 21170-21178.  
19061638 D.R.Southworth, and D.A.Agard (2008).
Species-dependent ensembles of conserved conformational states define the Hsp90 chaperone ATPase cycle.
  Mol Cell, 32, 631-640.  
18206974 E.J.Sacho, F.A.Kadyrov, P.Modrich, T.A.Kunkel, and D.A.Erie (2008).
Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha.
  Mol Cell, 29, 112-121.  
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.  
18242075 H.R.Saibil (2008).
Chaperone machines in action.
  Curr Opin Struct Biol, 18, 35-42.  
18462680 K.A.Krukenberg, F.Förster, L.M.Rice, A.Sali, and D.A.Agard (2008).
Multiple conformations of E. coli Hsp90 in solution: insights into the conformational dynamics of Hsp90.
  Structure, 16, 755-765.  
18400751 K.Richter, J.Soroka, L.Skalniak, A.Leskovar, M.Hessling, J.Reinstein, and J.Buchner (2008).
Conserved conformational changes in the ATPase cycle of human Hsp90.
  J Biol Chem, 283, 17757-17765.  
18373550 M.Sgobba, G.Degliesposti, A.M.Ferrari, and G.Rastelli (2008).
Structural models and binding site prediction of the C-terminal domain of human Hsp90: a new target for anticancer drugs.
  Chem Biol Drug Des, 71, 420-433.  
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.  
18591380 R.Rao, W.Fiskus, Y.Yang, P.Lee, R.Joshi, P.Fernandez, A.Mandawat, P.Atadja, J.E.Bradner, and K.Bhalla (2008).
HDAC6 inhibition enhances 17-AAG--mediated abrogation of hsp90 chaperone function in human leukemia cells.
  Blood, 112, 1886-1893.  
18478096 R.Srikakulam, L.Liu, and D.A.Winkelmann (2008).
Unc45b forms a cytosolic complex with Hsp90 and targets the unfolded myosin motor domain.
  PLoS ONE, 3, e2137.  
18462669 S.E.Jackson (2008).
The solution to multiple structures.
  Structure, 16, 659-661.  
18442971 S.K.Wandinger, K.Richter, and J.Buchner (2008).
The Hsp90 chaperone machinery.
  J Biol Chem, 283, 18473-18477.  
18347946 T.Kobayakawa, S.Yamada, A.Mizuno, and T.K.Nemoto (2008).
Substitution of only two residues of human Hsp90alpha causes impeded dimerization of Hsp90beta.
  Cell Stress Chaperones, 13, 97.  
18559531 Y.Yang, R.Rao, J.Shen, Y.Tang, W.Fiskus, J.Nechtman, P.Atadja, and K.Bhalla (2008).
Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion.
  Cancer Res, 68, 4833-4842.  
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
17964255 K.Richter, J.Reinstein, and J.Buchner (2007).
A Grp on the Hsp90 mechanism.
  Mol Cell, 28, 177-179.  
17277798 K.Richter, L.M.Hendershot, and B.C.Freeman (2007).
The cellular world according to Hsp90.
  Nat Struct Mol Biol, 14, 90-94.  
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.  
17925398 S.Frey, A.Leskovar, J.Reinstein, and J.Buchner (2007).
The ATPase cycle of the endoplasmic chaperone Grp94.
  J Biol Chem, 282, 35612-35620.  
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 code is shown on the right.