The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.

ATPases Associated with Diverse Cellular Activities/metabolism; Adaptor Proteins, Signal Transducing/metabolism; Antigens, Surface/metabolism; Apoptosis Regulatory Proteins/genetics/metabolism; Carrier Proteins/genetics/metabolism; Cell Line; DNA Helicases/metabolism; GTP-Binding Proteins/metabolism; HEK293 Cells; HSP90 Heat-Shock Proteins/metabolism; HeLa Cells; Humans; Male; Membrane Proteins/metabolism; Molecular Chaperones/metabolism; Protein Binding; Protein Folding; Protein Structure, Secondary; Signal Transduction; Testis/metabolism

Abstract :

[en] R2TP is an HSP90 co-chaperone that assembles important macro-molecular machineries. It is composed of an RPAP3-PIH1D1 heterodimer, which binds the two essential AAA+ATPases RUVBL1/RUVBL2. Here, we resolve the structure of the conserved C-terminal domain of RPAP3, and we show that it directly binds RUVBL1/RUVBL2 hexamers. The human genome encodes two other proteins bearing RPAP3-C-terminal-like domains and three containing PIH-like domains. Systematic interaction analyses show that one RPAP3-like protein, SPAG1, binds PIH1D2 and RUVBL1/2 to form an R2TP-like complex termed R2SP. This co-chaperone is enriched in testis and among 68 of the potential clients identified, some are expressed in testis and others are ubiquitous. One substrate is liprin-α2, which organizes large signaling complexes. Remarkably, R2SP is required for liprin-α2 expression and for the assembly of liprin-α2 complexes, indicating that R2SP functions in quaternary protein folding. Effects are stronger at 32 °C, suggesting that R2SP could help compensating the lower temperate of testis.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Maurizy, Chloé ; Université de Liège - ULiège > GIGA Stem Cells - Medical Chemistry

Quinternet, Marc

Abel, Yoann

Verheggen, Céline

Santo, Paulo E.

Bourguet, Maxime

Paiva, Ana C. F.

Bragantini, Benoît

Chagot, Marie-Eve

Robert, Marie-Cécile

More authors (12 more)

Language :

English

Title :

The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.

Publication date :

2018

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Issue :

Pages :

2093

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 10 May 2021

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