The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.
Fiche publication
Date publication
mai 2018
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHARPENTIER Bruno, Dr CIANFERANI Sarah, Dr MANIVAL Xavier
Tous les auteurs :
Maurizy C, Quinternet M, Abel Y, Verheggen C, Santo PE, Bourguet M, C F Paiva A, Bragantini B, Chagot ME, Robert MC, Abeza C, Fabre P, Fort P, Vandermoere F, M F Sousa P, Rain JC, Charpentier B, Cianférani S, Bandeiras TM, Pradet-Balade B, Manival X, Bertrand E
Lien Pubmed
Résumé
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.
Mots clés
ATPases Associated with Diverse Cellular Activities, metabolism, Adaptor Proteins, Signal Transducing, metabolism, Antigens, Surface, metabolism, Apoptosis Regulatory Proteins, genetics, Carrier Proteins, genetics, 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
Référence
Nat Commun. 2018 May 29;9(1):2093