Structural basis for phosphorylation-dependent recruitment of Tel2 to Hsp90 by Pih1

Mohinder Pal; Marc Morgan; Sarah E L Phelps; S Mark Roe; Sarah Parry-Morris; Jessica A Downs; Sigrun Polier; Laurence H Pearl; Chrisostomos Prodromou

doi:10.1016/j.str.2014.04.001

Structural basis for phosphorylation-dependent recruitment of Tel2 to Hsp90 by Pih1

Structure. 2014 Jun 10;22(6):805-18. doi: 10.1016/j.str.2014.04.001. Epub 2014 May 1.

Authors

Mohinder Pal¹, Marc Morgan¹, Sarah E L Phelps¹, S Mark Roe¹, Sarah Parry-Morris¹, Jessica A Downs¹, Sigrun Polier¹, Laurence H Pearl², Chrisostomos Prodromou³

Affiliations

¹ MRC Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
² MRC Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK. Electronic address: laurence.pearl@sussex.ac.uk.
³ MRC Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK. Electronic address: chris.prodromou@sussex.ac.uk.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallography, X-Ray
HSP90 Heat-Shock Proteins / chemistry*
HSP90 Heat-Shock Proteins / genetics
HSP90 Heat-Shock Proteins / metabolism*
Models, Molecular
Molecular Chaperones / chemistry
Molecular Chaperones / genetics
Molecular Chaperones / metabolism
Multiprotein Complexes / chemistry
Multiprotein Complexes / metabolism
Nuclear Proteins / chemistry*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Phosphorylation
Protein Binding
Protein Interaction Domains and Motifs
Protein Structure, Secondary
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Static Electricity
Telomere-Binding Proteins / chemistry*
Telomere-Binding Proteins / genetics
Telomere-Binding Proteins / metabolism*

Substances

HSP82 protein, S cerevisiae
HSP90 Heat-Shock Proteins
Molecular Chaperones
Multiprotein Complexes
Nuclear Proteins
PIH1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Tah1 protein, S cerevisiae
Tel2 protein, S cerevisiae
Telomere-Binding Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding