| Structural highlights
Function
[HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.[1] [2] [PIH1_YEAST] Involved in pre-rRNA processing and required for the NOP58-snoRNA interaction.[3]
Publication Abstract from PubMed
Client protein recruitment to the Hsp90 system depends on cochaperones that bind the client and Hsp90 simultaneously and facilitate their interaction. Hsp90 involvement in the assembly of snoRNPs, RNA polymerases, PI3-kinase-like kinases, and chromatin remodeling complexes depends on the TTT (Tel2-Tti1-Tti2), and R2TP complexes-consisting of the AAA-ATPases Rvb1 and Rvb2, Tah1 (Spagh/RPAP3 in metazoa), and Pih1 (Pih1D1 in humans)-that together provide the connection to Hsp90. The biochemistry underlying R2TP function is still poorly understood. Pih1 in particular, at the heart of the complex, has not been described at a structural level, nor have the multiple protein-protein interactions it mediates been characterized. Here we present a structural and biochemical analysis of Hsp90-Tah1-Pih1, Hsp90-Spagh, and Pih1D1-Tel2 complexes that reveal a domain in Pih1D1 specific for binding CK2 phosphorylation sites, and together define the structural basis by which the R2TP complex connects the Hsp90 chaperone system to the TTT complex.
Structural Basis for Phosphorylation-Dependent Recruitment of Tel2 to Hsp90 by Pih1.,Pal M, Morgan M, Phelps SE, Roe SM, Parry-Morris S, Downs JA, Polier S, Pearl LH, Prodromou C Structure. 2014 Apr 30. pii: S0969-2126(14)00105-1. doi:, 10.1016/j.str.2014.04.001. PMID:24794838[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
- ↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
- ↑ Gonzales FA, Zanchin NI, Luz JS, Oliveira CC. Characterization of Saccharomyces cerevisiae Nop17p, a novel Nop58p-interacting protein that is involved in Pre-rRNA processing. J Mol Biol. 2005 Feb 18;346(2):437-55. Epub 2004 Dec 21. PMID:15670595 doi:http://dx.doi.org/S0022-2836(04)01552-9
- ↑ Pal M, Morgan M, Phelps SE, Roe SM, Parry-Morris S, Downs JA, Polier S, Pearl LH, Prodromou C. Structural Basis for Phosphorylation-Dependent Recruitment of Tel2 to Hsp90 by Pih1. Structure. 2014 Apr 30. pii: S0969-2126(14)00105-1. doi:, 10.1016/j.str.2014.04.001. PMID:24794838 doi:http://dx.doi.org/10.1016/j.str.2014.04.001
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