3O4Z

Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes

3O4Z の概要

• エントリーDOI: 10.2210/pdb3o4z/pdb
• 分子名称: Telomere length regulation protein TEL2 (1 entity in total)
• 機能のキーワード: heat like helical repeats, protein binding
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast); 詳細
• 細胞内の位置: Nucleus : P53038
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 297383.69

構造登録者

Xie, Y.,Pavletich, N.P. (登録日: 2010-07-27, 公開日: 2010-09-15, 最終更新日: 2024-02-21)

主引用文献

Takai, H.,Xie, Y.,de Lange, T.,Pavletich, N.P.
Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.
Genes Dev., 24:2019-2030, 2010

PubMed Abstract: We reported previously that the stability of all mammalian phosphatidylinositol 3-kinase-related protein kinases (PIKKs) depends on their interaction with Tel2, the ortholog of yeast Tel2 and Caenorhabditis elegans Clk-2. Here we provide evidence that Tel2 acts with Hsp90 in the maturation of PIKK complexes. Quantitative immunoblotting showed that the abundance of Tel2 is low compared with the PIKKs, and Tel2 preferentially bound newly synthesized ATM, ATR, mTOR, and DNA-PKcs. Tel2 complexes contained, in addition to Tti1-Tti2, the Hsp90 chaperone, and inhibition of Hsp90 interfered with the interaction of Tel2 with the PIKKs. Analysis of in vivo labeled nascent protein complexes showed that Tel2 and Hsp90 mediate the formation of the mTOR TORC1 and TORC2 complexes and the association of ATR with ATRIP. The structure of yeast Tel2, reported here, shows that Tel2 consists of HEAT-like helical repeats that assemble into two separate α-solenoids. Through mutagenesis, we identify a surface patch of conserved residues involved in binding to the Tti1-Tti2 complex in vitro. In vivo, mutation of this conserved patch affects cell growth, levels of PIKKs, and ATM/ATR-mediated checkpoint signaling, highlighting the importance of Tti1-Tti2 binding to the function of Tel2. Taken together, our data suggest that the Tel2-Tti1-Tti2 complex is a PIKK-specific cochaperone for Hsp90.

PubMed: 20801936
DOI: 10.1101/gad.1956410

実験手法

X-RAY DIFFRACTION (3.1 Å)