Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone.

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)-li...

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Detalhes bibliográficos
Autores: Pal, Mohinder, Muñoz-Hernandez, Hugo, Bjorklund, Dennis, Zhou, Lihong, Degliesposti, Gianluca, Skehel, J Mark, Hesketh, Emma L, Thompson, Rebecca F, Pearl, Laurence H, Llorca Blanco, Oscar Antonio, Prodromou, Chrisostomos
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/23082
Acesso em linha:https://hdl.handle.net/20.500.12105/23082
Access Level:acceso abierto
Palavra-chave:Adenosine Triphosphatases
Cryoelectron Microscopy
Humans
Models, Molecular
Molecular Chaperones
Multiprotein Complexes
Protein Binding
Protein Domains
Protein Interaction Mapping
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Structure-Activity Relationship
Descrição
Resumo: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.

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