7F4U

Cryo-EM structure of TELO2-TTI1-TTI2 complex

Summary for 7F4U

• Entry DOI: 10.2210/pdb7f4u/pdb
• EMDB information: 31454
• Descriptor: Telomere length regulation protein TEL2 homolog, TELO2-interacting protein 1 homolog, TELO2-interacting protein 2 (3 entities in total)
• Functional Keywords: adaptor, chaperone, telo2, tti1, tti2
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 263915.58

Authors

Cho, Y.,Kim, Y. (deposition date: 2021-06-21, release date: 2022-06-22, Last modification date: 2024-06-12)

Primary citation

Kim, Y.,Park, J.,Joo, S.Y.,Kim, B.G.,Jo, A.,Lee, H.,Cho, Y.
Structure of the Human TELO2-TTI1-TTI2 Complex.
J.Mol.Biol., 434:167370-167370, 2022

PubMed Abstract: Phosphatidylinositol 3-kinase-related protein kinases (PIKKs) play critical roles in various metabolic pathways related to cell proliferation and survival. The TELO2-TTI1-TTI2 (TTT) complex has been proposed to recognize newly synthesized PIKKs and to deliver them to the R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) and the heat shock protein 90 chaperone, thereby supporting their folding and assembly. Here, we determined the cryo-EM structure of the TTT complex at an average resolution of 4.2 Å. We describe the full-length structures of TTI1 and TELO2, and a partial structure of TTI2. All three proteins form elongated helical repeat structures. TTI1 provides a platform on which TELO2 and TTI2 bind to its central region and C-terminal end, respectively. The TELO2 C-terminal domain (CTD) is required for the interaction with TTI1 and recruitment of Ataxia-telangiectasia mutated (ATM). The N- and C-terminal segments of TTI1 recognize the FRAP-ATM-TRRAP (FAT) domain and the N-terminal HEAT repeats of ATM, respectively. The TELO2 CTD and TTI1 N- and C-terminal segments are required for cell survival in response to ionizing radiation.

PubMed: 34838521
DOI: 10.1016/j.jmb.2021.167370

Experimental method

ELECTRON MICROSCOPY (4.2 Å)