6ZWO

cryo-EM structure of human mTOR complex 2, focused on one half

6ZWO の概要

• エントリーDOI: 10.2210/pdb6zwo/pdb
• 関連するPDBエントリー: 6ZWM
• EMDBエントリー: 11489 11490 11491 11492
• 分子名称: Serine/threonine-protein kinase mTOR, Target of rapamycin complex subunit LST8, Rapamycin-insensitive companion of mTOR, ... (8 entities in total)
• 機能のキーワード: mtor, kinase, complex, inositol, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 578532.52

構造登録者

Scaiola, A.,Mangia, F.,Imseng, S.,Boehringer, D.,Ban, N.,Maier, T. (登録日: 2020-07-28, 公開日: 2020-11-18)

主引用文献

Scaiola, A.,Mangia, F.,Imseng, S.,Boehringer, D.,Berneiser, K.,Shimobayashi, M.,Stuttfeld, E.,Hall, M.N.,Ban, N.,Maier, T.
The 3.2- angstrom resolution structure of human mTORC2.
Sci Adv, 6:-, 2020

PubMed Abstract: The protein kinase mammalian target of rapamycin (mTOR) is the central regulator of cell growth. Aberrant mTOR signaling is linked to cancer, diabetes, and neurological disorders. mTOR exerts its functions in two distinct multiprotein complexes, mTORC1 and mTORC2. Here, we report a 3.2-Å resolution cryo-EM reconstruction of mTORC2. It reveals entangled folds of the defining Rictor and the substrate-binding SIN1 subunits, identifies the carboxyl-terminal domain of Rictor as the source of the rapamycin insensitivity of mTORC2, and resolves mechanisms for mTORC2 regulation by complex destabilization. Two previously uncharacterized small-molecule binding sites are visualized, an inositol hexakisphosphate (InsP6) pocket in mTOR and an mTORC2-specific nucleotide binding site in Rictor, which also forms a zinc finger. Structural and biochemical analyses suggest that InsP6 and nucleotide binding do not control mTORC2 activity directly but rather have roles in folding or ternary interactions. These insights provide a firm basis for studying mTORC2 signaling and for developing mTORC2-specific inhibitors.

PubMed: 33158864
DOI: 10.1126/sciadv.abc1251

実験手法

ELECTRON MICROSCOPY (3 Å)