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.
The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.
Maurizy C., Quinternet M., Abel Y., Verheggen C.,. Santo P E, Bourguet M., Paiva A.C.F., Bragantini B., Chagot M-E., Robert M-C., Abeza C., Fabre P., Fort P., Vandermoere F, Sousa P.M. F., Rain J-C., Charpentier B., Bandeiras T-M., Cianférani S., Pradet-Balade B., Manival X., Bertrand E.
2018 May 29 / vol 9(1) / pages 2093
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