Molecular organization of target of rapamycin complex 2.
The target of rapamycin (TOR), a highly conserved serine/threonine kinase, plays a central role in the control of eukaryotic cell growth. TOR exists in two functionally and structurally distinct complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TORC1 controls cell growth via a rapamycin-sensitive signaling branch regulating translation, transcription, nutrient uptake, ribosome biogenesis, and autophagy. TORC2 controls the organization of the actin cytoskeleton through a rapamycin-insensitive signaling branch and in yeast consists of the six proteins AVO1, AVO2, AVO3, BIT61, LST8, and TOR2. Here we have focused on the characterization of TORC2. Our studies suggest that TORC2 is oligomeric, likely a TORC2-TORC2 dimer. AVO1 and AVO3 bind cooperatively to the N-terminal HEAT repeat region in TOR2 and are required for TORC2 integrity. AVO2 is a nonessential peripheral protein associated with AVO1 and AVO3. LST8 binds separately to the C-terminal kinase domain region in TOR2 and appears to modulate both the integrity and kinase activity of TORC2. TORC2 autophosphorylates sites in AVO1 and AVO3, but TORC2 kinase activity is not required for TORC2 integrity. We have demonstrated that mammalian TOR is also oligomeric. The architecture of TORC2 is discussed in the context of TORC2 assembly and regulation.
Division of Biochemistry, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Stephan
S
Wullschleger
Robbie
R
Loewith
Wolfgang
W
Oppliger
Michael N
MN
Hall
D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D019869:Phosphatidylinositol 3-Kinases; D029701:Saccharomyces cerevisiae Proteins; C503706:Avo1 protein, S cerevisiae; C503707:Avo2 protein, S cerevisiae; C110280:LST8 protein, S cerevisiae; C504817:TSC11 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae