2. Academic Validation
  3. Architecture of human mTOR complex 1

Architecture of human mTOR complex 1

  • Science. 2016 Jan 1;351(6268):48-52. doi: 10.1126/science.aaa3870.
Christopher H S Aylett 1,  Evelyn Sauer 2,  Stefan Imseng 2,  Daniel Boehringer 1,  Michael N Hall 3,  Nenad Ban 4,  Timm Maier 3
Affiliations

Affiliations

  • 1 Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland.
  • 2 Biozentrum, University of Basel, Basel, Switzerland.
  • 3 Biozentrum, University of Basel, Basel, Switzerland. ban@mol.biol.ethz.ch m.hall@unibas.ch timm.maier@unibas.ch.
  • 4 Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland. ban@mol.biol.ethz.ch m.hall@unibas.ch timm.maier@unibas.ch.
PMID: 26678875 DOI: 10.1126/science.aaa3870
Abstract

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.

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