Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Regulation of human mTOR complexes by DEPTOR.
Journal, issue, pages	Elife, Vol. 10, Year 2021
Publish date	Sep 14, 2021
Authors	Matthias Wälchli / Karolin Berneiser / Francesca Mangia / Stefan Imseng / Louise-Marie Craigie / Edward Stuttfeld / Michael N Hall / Timm Maier /
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 ...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.
External links	Elife / PubMed:34519268 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.93 - 4.24 Å
Structure data	13347 7pe7 EMDB-13347, PDB-7pe7: cryo-EM structure of DEPTOR bound to human mTOR complex 2, overall refinement Method: EM (single particle) / Resolution: 3.41 Å 13348 7pe8 EMDB-13348, PDB-7pe8: cryo-EM structure of DEPTOR bound to human mTOR complex 2, focussed on one protomer Method: EM (single particle) / Resolution: 3.2 Å 13349 7pe9 EMDB-13349, PDB-7pe9: cryo-EM structure of DEPTOR bound to human mTOR complex 2, DEPt-bound subset local refinement Method: EM (single particle) / Resolution: 3.7 Å 13350 7pea EMDB-13350, PDB-7pea: cryo-EM structure of DEPTOR bound to human mTOR complex 1, overall refinement Method: EM (single particle) / Resolution: 4.07 Å 13351 7peb EMDB-13351, PDB-7peb: cryo-EM structure of DEPTOR bound to human mTOR complex 1, focussed on one protomer Method: EM (single particle) / Resolution: 3.67 Å 13352 7pec EMDB-13352, PDB-7pec: cryo-EM structure of DEPTOR bound to human mTOR complex 1, DEPt-bound subset local refinement Method: EM (single particle) / Resolution: 4.24 Å PDB-7ped: DEPTOR DEP domain tandem (DEPt) Method: X-RAY DIFFRACTION / Resolution: 1.93 Å
Chemicals	ChemComp-IHP: INOSITOL HEXAKISPHOSPHATE ChemComp-ZN: Unknown entry ChemComp-ACE: ACETYL GROUP ChemComp-HOH: WATER
Source	homo sapiens (human)
Keywords	SIGNALING PROTEIN / DEPTOR / mTOR / regulator / inhibitor / mTORC2 / DEP-domain / PDZ-domain / mTORC1 / mTOR-binding