6EZ4

NMR structure of the C-terminal domain of the human RPAP3 protein

Summary for 6EZ4

• Entry DOI: 10.2210/pdb6ez4/pdb
• NMR Information: BMRB: 34200
• Descriptor: RNA polymerase II-associated protein 3 (1 entity in total)
• Functional Keywords: rvb1, rvb2, ruvbl1, ruvbl2, rna polymerase, r2tp, snornp, pih, chaperone
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15804.36

Authors

Fabre, P.,Chagot, M.E.,Bragantini, B.,Manival, X.,Quinternet, M. (deposition date: 2017-11-14, release date: 2018-04-18, Last modification date: 2024-01-17)

Primary citation

Maurizy, C.,Quinternet, M.,Abel, Y.,Verheggen, C.,Santo, P.E.,Bourguet, M.,C F Paiva, A.,Bragantini, B.,Chagot, M.E.,Robert, M.C.,Abeza, C.,Fabre, P.,Fort, P.,Vandermoere, F.,M F Sousa, P.,Rain, J.C.,Charpentier, B.,Cianferani, S.,Bandeiras, T.M.,Pradet-Balade, B.,Manival, X.,Bertrand, E.
The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.
Nat Commun, 9:2093-2093, 2018

PubMed 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.

PubMed: 29844425
DOI: 10.1038/s41467-018-04431-1

Experimental method

SOLUTION NMR