Hsp90

Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
Solid ribbon model of the yeast Hsp90-dimer (α-helices = red, β-sheets = cyan, loops = grey) in complex with ATP (red stick diagram).[1]
Identifiers
SymbolHATPase_c
PfamPF02518
Pfam clanCL0025
InterProIPR003594
SMARTSM00387
SCOP21ei1 / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Hsp90 protein
Structure of the N-terminal domain of the yeast Hsp90 chaperone.[2]
Identifiers
SymbolHsp90
PfamPF00183
InterProIPR020576
PROSITEPDOC00270
SCOP21ah6 / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Domain structure of the yeast heat-inducible Hsp90. Top: Crystallographic structure of the dimeric Hsp90.[1] Bound ATP molecules are represented by space filling spheres. Bottom: 1D sequence of the yeast Hsp90. NTD= N-terminal domain (red), MD = middle domain (green), CTD = C-terminal domain (blue).
Crystallographic structure of the ATP binding pocket of Hsp90 where ATP is represented by a ball and stick figure (carbon atoms = grey, nitrogen = blue, oxygen = red, phosphorus = orange) and Hsp90 is depicted as a solid surface (negatively charged = red, positively charged = blue, electrostatically neutral = grey).[1]
Pincer movement of Hsp90 coupled to the ATPase cycle. NTD = N-terminal domain, MD = middle domain, CTD = C-terminal domain.
The Hsp90 chaperone cycle. X/Y represents an immature incompletely folded protein such a steroid receptor. Hsp40, Hsp70, and p23 are partner chaperones while Hop is a co-chaperone. Also, X-X represents a mature properly folded protein dimer.

Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.

Heat shock proteins, as a class, are among the most highly expressed cellular proteins across all species.[3] As their name implies, heat shock proteins protect cells when stressed by elevated temperatures. They account for 1–2% of total protein in unstressed cells. However, when cells are heated, the fraction of heat shock proteins increases to 4–6% of cellular proteins.[4]

Heat shock protein 90 (Hsp90) is one of the most common of the heat-related proteins. The "90" comes from the fact that it has a mass of roughly 90 kilodaltons. A 90 kDa protein is considered fairly large for a non-fibrous protein. Hsp90 is found in bacteria and all branches of eukarya, but it is apparently absent in archaea.[5] Whereas cytoplasmic Hsp90 is essential for viability under all conditions in eukaryotes, the bacterial homologue HtpG is dispensable under non-heat stress conditions.[6]

This protein was first isolated by extracting proteins from cells stressed by heating, dehydrating or by other means, all of which caused the cell's proteins to begin to denature.[7] However it was later discovered that Hsp90 also has essential functions in unstressed cells.

  1. ^ a b c PDB: 2CG9​; Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C, Pearl LH (April 2006). "Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex". Nature. 440 (7087): 1013–7. doi:10.1038/nature04716. PMC 5703407. PMID 16625188.
  2. ^ Prodromou C, Roe SM, Piper PW, Pearl LH (June 1997). "A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone". Nat. Struct. Biol. 4 (6): 477–82. doi:10.1038/nsb0697-477. PMID 9187656. S2CID 38764610.
  3. ^ Csermely P, Schnaider T, Soti C, Prohászka Z, Nardai G (August 1998). "The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review". Pharmacol. Ther. 79 (2): 129–68. doi:10.1016/S0163-7258(98)00013-8. PMID 9749880.
  4. ^ Crevel G, Bates H, Huikeshoven H, Cotterill S (1 June 2001). "The Drosophila Dpit47 protein is a nuclear Hsp90 co-chaperone that interacts with DNA polymerase alpha". J. Cell Sci. 114 (Pt 11): 2015–25. doi:10.1242/jcs.114.11.2015. PMID 11493638.
  5. ^ Chen B, Zhong D, Monteiro A (2006). "Comparative genomics and evolution of the HSP90 family of genes across all kingdoms of organisms". BMC Genomics. 7: 156. doi:10.1186/1471-2164-7-156. PMC 1525184. PMID 16780600.
  6. ^ Thomas JG, Baneyx F (October 1998). "Roles of the Escherichia coli Small Heat Shock Proteins IbpA and IbpB in Thermal Stress Management: Comparison with ClpA, ClpB, and HtpG In Vivo". J. Bacteriol. 180 (19): 5165–72. doi:10.1128/JB.180.19.5165-5172.1998. PMC 107554. PMID 9748451.
  7. ^ Prodromou C, Panaretou B, Chohan S, Siligardi G, O'Brien R, Ladbury JE, Roe SM, Piper PW, Pearl LH (August 2000). "The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains". EMBO J. 19 (16): 4383–92. doi:10.1093/emboj/19.16.4383. PMC 302038. PMID 10944121.