2026-07-21T14:19:54Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/230822024-11-29T20:15:43Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Pal, Mohinder
author
Muñoz-Hernandez, Hugo
author
Bjorklund, Dennis
author
Zhou, Lihong
author
Degliesposti, Gianluca
author
Skehel, J Mark
author
Hesketh, Emma L
author
Thompson, Rebecca F
author
Pearl, Laurence H
author
Llorca Blanco, Oscar Antonio
author
Prodromou, Chrisostomos
funder
Wellcome Trust
funder
University of Leeds (Reino Unido)
funder
UK Research and Innovation
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Instituto de Salud Carlos III
2024-09-16T08:16:56Z
2024-09-16T08:16:56Z
2021-07-06
Cell Rep . 2021 ;36(1):109317.
10.1016/j.celrep.2021.109317
2211-1247
Cell reports
34233195
https://hdl.handle.net/20.500.12105/23082
The R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) complex, in collaboration with heat shock protein 90 (HSP90), functions as a chaperone for the assembly and stability of protein complexes, including RNA polymerases, small nuclear ribonucleoprotein particles (snRNPs), and phosphatidylinositol 3-kinase (PI3K)-like kinases (PIKKs) such as TOR and SMG1. PIKK stabilization depends on an additional complex of TELO2, TTI1, and TTI2 (TTT), whose structure and function are poorly understood. The cryoelectron microscopy (cryo-EM) structure of the human R2TP-TTT complex, together with biochemical experiments, reveals the mechanism of TOR recruitment to the R2TP-TTT chaperone. The HEAT-repeat TTT complex binds the kinase domain of TOR, without blocking its activity, and delivers TOR to the R2TP chaperone. In addition, TTT regulates the R2TP chaperone by inhibiting RUVBL1-RUVBL2 ATPase activity and by modulating the conformation and interactions of the PIH1D1 and RPAP3 components of R2TP. Taken together, our results show how TTT couples the recruitment of TOR to R2TP with the regulation of this chaperone system.
eng
Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone.
research article