Abstract
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
Substances
-
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