4.8 Article

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

Journal

CELL REPORTS
Volume 36, Issue 1, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.109317

Keywords

-

Categories

Funding

  1. Wellcome Trust [095605/Z/11/A, 108466/Z/15/Z, 095605/Z/11/Z]
  2. RM Phillips Trust
  3. University of Leeds ABSL award
  4. MRC
  5. BBSRC [BB/R01678X/1]
  6. Spanish Ministry of Science and Innovation/Agencia Estatal de Investigacion (MCI/AEI) - European Regional Development Fund (ERDF) [SAF2017-82632-P]
  7. Autonomous Region of Madrid - European Social Fund
  8. European Regional Development Fund [Y2018/BIO4747, P2018/NMT4443]
  9. National Institute of Health Carlos III
  10. BBSRC [BB/R01678X/1] Funding Source: UKRI
  11. Wellcome Trust [095605/Z/11/A, 095605/Z/11/Z] Funding Source: Wellcome Trust

Ask authors/readers for more resources

The R2TP complex, in collaboration with HSP90, functions as a chaperone for the assembly and stability of protein complexes, with the stability of PIKKs like TOR depending on the TTT complex. TTT regulates the R2TP chaperone by inhibiting RUVBL1-RUVBL2 ATPase activity and modulating the conformation and interactions of PIH1D1 and RPAP3 components.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available