Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person The chaperoning function of HSP90 is coupled to its ATPase a...
| Class:Id | Summation:8948955 |
|---|---|
| _displayName | The chaperoning function of HSP90 is coupled to its ATPase a... |
| _timestamp | 2016-11-19 00:46:27 |
| created | [InstanceEdit:8948954] Shamovsky, Veronica, 2016-11-19 |
| literatureReference | [LiteratureReference:8938575] Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions [LiteratureReference:8938593] Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery [LiteratureReference:8938533] Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex [LiteratureReference:8938565] The 'active life' of Hsp90 complexes [LiteratureReference:8938520] The ATPase cycle of Hsp90 drives a molecular 'clamp' via transient dimerization of the N-terminal domains [LiteratureReference:8938576] Conserved conformational changes in the ATPase cycle of human Hsp90 [LiteratureReference:3371482] A common conformationally coupled ATPase mechanism for yeast and human cytoplasmic HSP90s [LiteratureReference:8938540] Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90 [LiteratureReference:8936944] Structural characterization of the substrate transfer mechanism in Hsp70/Hsp90 folding machinery mediated by Hop [LiteratureReference:3371446] Client-loading conformation of the Hsp90 molecular chaperone revealed in the cryo-EM structure of the human Hsp90:Hop complex [LiteratureReference:8938549] Stimulation of the weak ATPase activity of human hsp90 by a client protein |
| text | The chaperoning function of HSP90 is coupled to its ATPase activity. Our current understanding of the ATPase mechanism of Hsp90 is based largely on structural and functional studied for the Saccharomyces cerevisiae Hsp90 complexes (Meyer P et al. 2003, 2004; Ali MM et al. 2006; Prodromou C et al. 2000; Prodromou C 2012). The ATPase cycle of human HSP90 is less well understood, however several studies suggest that the underlying enzymatic mechanisms and a set of conformational changes that accompany the ATPase cycle are highly similar in both species (Richter K et al. 2008; Vaughan CK et al. 2009). 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 N-terminal domain (NTD) (Ali MM et al. 2006; Prodromou C et al. 2000; Chadli A et al. 2000). The association of ATP with NTD then stimulates structural changes in NTD and in the middle domain that are likely to involve movements of the ATP lid segment within each N-terminal domain that locates over the bound ATP. 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). Furthermore, the intrachain associations of NTD with the middle domain leads to the active conformation of the catalytic loop of HSP90, which commits the ATP for hydrolysis (Meyer P et al. 2003). 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). In addition, client protein binding to HSP90 was found to increase ATPase activity of HSP90 up to 200-fold (McLaughlin SH et al. 2002). After hydrolysis of ATP the ligand-bound steroid hormone receptor (SHR) is released from HSP90 complex. The Reactome module describes ATPase activity of HSP90 in the nucleus, however it is not entirely clear whether cytosolic hormone-bound SHR translocates through the nuclear pores before or after ATP-dependent dissociation from the HSP90 complex. |
| (summation) | [BlackBoxEvent:5618093] ATP hydrolysis by HSP90 [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by The chaperoning function of HSP90 is coupled to its ATPase a... (8948955)
