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TitleArchitecture of human mTOR complex 1.
Journal, issue, pagesScience, Vol. 351, Issue 6268, Page 48-52, Year 2016
Publish dateJan 1, 2016
AuthorsChristopher H S Aylett / Evelyn Sauer / Stefan Imseng / Daniel Boehringer / Michael N Hall / Nenad Ban / Timm Maier /
PubMed AbstractTarget of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of ...Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site.
External linksScience / PubMed:26678875
MethodsEM (single particle) / X-ray diffraction
Resolution4.3 - 6.1 Å
Structure data

EMDB-3212:
Architecture of human mTOR Complex 1 - 6.1 Angstrom reconstruction
Method: EM (single particle) / Resolution: 6.1 Å

3213

5flc

EMDB-3213, PDB-5flc:
Architecture of human mTOR Complex 1 - 5.9 Angstrom reconstruction
Method: EM (single particle) / Resolution: 5.9 Å

PDB-5ef5:
Crystal structure of Chaetomium thermophilum Raptor
Method: X-RAY DIFFRACTION / Resolution: 4.3 Å

Chemicals

ChemComp-RAP:
RAPAMYCIN IMMUNOSUPPRESSANT DRUG / immunosuppressant, antibiotic*YM

Source
  • homo sapiens (human)
  • chaetomium thermophilum (fungus)
  • spodoptera frugiperda (fall armyworm)
KeywordsSIGNALING PROTEIN / mTORC1 / Target of Rapamycin / Raptor / Rptor / TRANSFERASE / RAPAMYCIN

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