Structure of TOR and its complex with KOG1

Mol Cell. 2007 Aug 3;27(3):509-16. doi: 10.1016/j.molcel.2007.05.040.


The target of rapamycin (TOR) is a large (281 kDa) conserved Ser/Thr protein kinase that functions as a central controller of cell growth. TOR assembles into two distinct multiprotein complexes: TORC1 and TORC2. A defining feature of TORC1 is the interaction of TOR with KOG1 (Raptor in mammals) and its sensitivity to a rapamycin-FKBP12 complex. Here, we have reconstructed in three dimensions the 25 A resolution structures of endogenous budding yeast TOR1 and a TOR-KOG1 complex, using electron microscopy. TOR features distinctive N-terminal HEAT repeats that form a curved tubular-shaped domain that associates with the C-terminal WD40 repeat domain of KOG1. The N terminus of KOG1 is in proximity to the TOR kinase domain, likely functioning to bring substrates into the vicinity of the catalytic region. A model is proposed for the molecular architecture of the TOR-KOG1 complex explaining its sensitivity to rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / chemistry*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / ultrastructure
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / ultrastructure
  • Protein Conformation
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / ultrastructure
  • Sirolimus / metabolism


  • Intracellular Signaling Peptides and Proteins
  • Kog1 protein, S cerevisiae
  • LST8 protein, S cerevisiae
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • Sirolimus