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Details on Person The molecular chaperone heat-shock protein 90 (HSP90) functi...
| Class:Id | Summation:8938541 |
|---|---|
| _displayName | The molecular chaperone heat-shock protein 90 (HSP90) functi... |
| _timestamp | 2016-11-19 00:53:45 |
| created | [InstanceEdit:8938553] Shamovsky, Veronica, 2016-09-09 |
| literatureReference | [LiteratureReference:8938591] Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90 [LiteratureReference:8938561] Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone [LiteratureReference:8938581] Understanding ligand-based modulation of the Hsp90 molecular chaperone dynamics at atomic resolution [LiteratureReference:1218826] Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent [LiteratureReference:8938564] Structure and mechanism of the Hsp90 molecular chaperone machinery [LiteratureReference:8937300] In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis [LiteratureReference:8937335] The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation [LiteratureReference:8938575] Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions [LiteratureReference:8938533] Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex [LiteratureReference:8938520] The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains [LiteratureReference:8938593] Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery [LiteratureReference:8938565] The 'active life' of Hsp90 complexes [LiteratureReference:8936890] Structure, function and regulation of the hsp90 machinery [LiteratureReference:8938556] Conformational dynamics of the molecular chaperone Hsp90 [LiteratureReference:3371446] Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex [LiteratureReference:8936944] Structural characterization of the substrate transfer mechanism in Hsp70/Hsp90 folding machinery mediated by Hop [LiteratureReference:8938540] Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90 [LiteratureReference:5324657] N-terminal domain of human Hsp90 triggers binding to the cochaperone p23 |
| modified | [InstanceEdit:8948991] Shamovsky, Veronica, 2016-11-19 |
| text | The molecular chaperone heat-shock protein 90 (HSP90) functions as a homodimer. Each HSP90 protomer contains three flexibly linked regions, the N-terminal ATP-binding domain (NTD), the middle domain, and the C-terminal dimerization domain (Prodromou C et al. 1997; Pearl LH and Prodromou C 2006). HSP90 dimer is rather a dynamic molecule and ATP binding and hydrolysis are associated with conformational changes (Obermann WM et al. 1998; Krukenberg KA et al. 2011; Li J & Buchner J 2013; Prodromou C 2012). The structures of the isolated yeast and human N-terminal domain (NTD) of HSP90 bound to ATP, ADP and adenylylimidodiphosphate (AMP-PNP, a non-hydrolysable analogue of ATP) suggest that nucleotides bind deep in the cleft of NTD in open apo state of HSP90 (Prodromou C et al.1997; Meyer P et al. 2003, 2004; Colombo G et al. 2008; Li J et al. 2012). The structural studies of NTD of human HSP90 with antitumor agent geldanamycin (that acts as an ADP/ATP mimetic) support the polar interactions in the binding pocket described for yeast Hsp90 and ADP or ATP (Stebbins CE et al. 1997; Prodromou C et al.1997; Grenert JP et al. 1997). Once ATP is bound it helps to stabilize the closed ATP lid state, in which the gamma-phosphate of ATP provides a hydrogen bonding that promotes a stable association of the ATP lid with NTD. The association of ATP or AMP-PNP with NTD then stimulates structural changes in NTD. NMR analysis of human full-length HSP90 protein with and without ATP confirmed that ATP binding led to conformational changes in NTD (Karagöz GE et al. 2010). No structural changes were observed in the middle and C-terminal domains (Karagöz GE et al. 2010). However, other studies suggest that ATP-dependent conformational changes occur both in NTD and in the middle domain of HSP90 (Ali MM et al. 2006; Prodromou C et al. 2000; Chadli A et al. 2000; Meyer P et al. 2003). The changes are likely to involve movements of the ATP lid segment within each N-terminal domain that locates over the bound ATP (Ali MM et al. 2006; Prodromou C et al. 2000; Chadli A et al. 2000). The movement of the lids exposes surface residues that are subsequently involved in transient dimerization of the N-terminal domains of HSP90 (Ali MM et al. 2006; Prodromou C et al. 2000; Chadli A et al. 2000). The subsequent conformational changes upon ATP binding are regulated by co-chaperone activities. For example, arrangement of the STIP1 domains in the complex seems to prevent the NTDs dimerization of HSP90 monomers and total closure of the HSP90 dimer that is required for an efficient HSP90-mediated ATP hydrolysis (Southworth DR & Agard DA 2011; Alvira S et al. 2014). Thus, ATP binding coupled to co-chaperone-mediated loading of client protein to HSP90 complex regulates ATPase activity of HSP90. |
| (summation) | [Reaction:5618107] ATP binding to HSP90 triggers conformation change [Homo sapiens] |
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