Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2

Nat Commun. 2017 Nov 23;8(1):1729. doi: 10.1038/s41467-017-01862-0.


The target of rapamycin (TOR) kinase assembles into two distinct multiprotein complexes, conserved across eukaryote evolution. In contrast to TOR complex 1 (TORC1), TORC2 kinase activity is not inhibited by the macrolide rapamycin. Here, we present the structure of Saccharomyces cerevisiae TORC2 determined by electron cryo-microscopy. TORC2 contains six subunits assembling into a 1.4 MDa rhombohedron. Tor2 and Lst8 form the common core of both TOR complexes. Avo3/Rictor is unique to TORC2, but interacts with the same HEAT repeats of Tor2 that are engaged by Kog1/Raptor in mammalian TORC1, explaining the mutual exclusivity of these two proteins. Density, which we conclude is Avo3, occludes the FKBP12-rapamycin-binding site of Tor2's FRB domain rendering TORC2 rapamycin insensitive and recessing the kinase active site. Although mobile, Avo1/hSin1 further restricts access to the active site as its conserved-region-in-the-middle (CRIM) domain is positioned along an edge of the TORC2 active-site-cleft, consistent with a role for CRIM in substrate recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carrier Proteins / chemistry
  • Cryoelectron Microscopy
  • Mechanistic Target of Rapamycin Complex 2 / chemistry*
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / ultrastructure*
  • Models, Molecular
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Transcription Factors / ultrastructure


  • Avo1 protein, S cerevisiae
  • Carrier Proteins
  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • TSC11 protein, S cerevisiae
  • Transcription Factors
  • Mechanistic Target of Rapamycin Complex 2