The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones

Nature Communications
Chloé MaurizyEdouard Bertrand

Abstract

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.

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Citations

May 24, 2019·The Biochemical Journal·Marie-Eve ChagotMarc Quinternet
May 23, 2019·Molecular Biology of the Cell·Ramila S Patel-KingStephen M King
Dec 11, 2019·International Journal of Molecular Sciences·Hanna Fabczak, Anna Osinka
Jul 29, 2018·Nature Communications·Benoit CoulombeMarie-Soleil Gauthier
Nov 18, 2019·Biophysics Reviews·Thiago V SeraphimWalid A Houry
Nov 1, 2020·Current Opinion in Structural Biology·Maria I DaudenOscar Llorca
Dec 7, 2020·Seminars in Cell & Developmental Biology·Marie LegendreHannah M Mitchison
Mar 25, 2019·Methods : a Companion to Methods in Enzymology·Katlyn Hughes Burriss, Amber L Mosley
Jan 1, 2020·The Japanese Dental Science Review·Yoshito KakiharaMakio Saeki
Jun 17, 2021·Nature Communications·Klára KlimešováDavid Staněk
Aug 4, 2021·Journal of Cell Science·Stephen M King
Aug 12, 2021·Nature Communications·Chloé MaurizyBérengère Pradet-Balade
Mar 17, 2020·Journal of Chemical Information and Modeling·Carlos F RodríguezOscar Llorca

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Datasets Mentioned

BETA
CCDC103

Methods Mentioned

BETA
protein folding
NMR
two-hybrid
gel-filtration
co-IP
Y2H
fluorescence microscopy
size exclusion chromatography
chips
chip

Software Mentioned

MassLynx
Geneious
Annotation
AMBER Portal Server for NMR AMPS
AMBER
BLAST
MaxQuant
DALI
LUMIER
- NMR

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