7PED

DEPTOR DEP domain tandem (DEPt)

7PED の概要

• エントリーDOI: 10.2210/pdb7ped/pdb
• 分子名称: DEP domain-containing mTOR-interacting protein (2 entities in total)
• 機能のキーワード: dep-domain, mtor-binding, mtor, mtorc1, mtorc2, deptor, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54257.85

構造登録者

Waelchli, M.,Jakob, R.,Maier, T. (登録日: 2021-08-09, 公開日: 2021-09-08, 最終更新日: 2024-11-20)

主引用文献

Walchli, M.,Berneiser, K.,Mangia, F.,Imseng, S.,Craigie, L.M.,Stuttfeld, E.,Hall, M.N.,Maier, T.
Regulation of human mTOR complexes by DEPTOR.
Elife, 10:-, 2021

PubMed Abstract: The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein that binds and regulates both complexes of mammalian target of rapamycin (mTOR), a central regulator of cell growth. Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. The PDZ domain binds tightly with mildly activating effect, but then acts as an anchor for DEPt association that allosterically suppresses mTOR activation. The binding interfaces of the PDZ domain and DEPt also support further regulation by other signaling pathways. A separate, substrate-like mode of interaction for DEPTOR phosphorylation by mTOR complexes rationalizes inhibition of non-stimulated mTOR activity at higher DEPTOR concentrations. The multifaceted interplay between DEPTOR and mTOR provides a basis for understanding the divergent roles of DEPTOR in physiology and opens new routes for targeting the mTOR-DEPTOR interaction in disease.

PubMed: 34519268
DOI: 10.7554/eLife.70871

実験手法

X-RAY DIFFRACTION (1.93 Å)