7OLE

Cryo-EM structure of the TELO2-TTI1-TTI2-RUVBL1-RUVBL2 complex

Summary for 7OLE

• Entry DOI: 10.2210/pdb7ole/pdb
• EMDB information: 12979 4287
• Descriptor: RuvB-like 1, RuvB-like 2, TELO2-interacting protein 1 homolog,TELO2-interacting protein 1 homolog,TTI1, ... (6 entities in total)
• Functional Keywords: r2tp, ttt, telo2, tti1, tti2, ruvbl1, ruvbl2, hsp90 chaperone, mtor, pikk, structural protein, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 9
• Total formula weight: 632596.46

Authors

Pal, M.,Llorca, O.,Pearl, L. (deposition date: 2021-05-19, release date: 2021-07-07, Last modification date: 2025-10-01)

Primary citation

Pal, M.,Munoz-Hernandez, H.,Bjorklund, D.,Zhou, L.,Degliesposti, G.,Skehel, J.M.,Hesketh, E.L.,Thompson, R.F.,Pearl, L.H.,Llorca, O.,Prodromou, C.
Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone.
Cell Rep, 36:109317-109317, 2021

PubMed Abstract: 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.

PubMed: 34233195
DOI: 10.1016/j.celrep.2021.109317

Experimental method

ELECTRON MICROSCOPY (3.41 Å)