RRC ID 47682
著者 Tatebe H, Murayama S, Yonekura T, Hatano T, Richter D, Furuya T, Kataoka S, Furuita K, Kojima C, Shiozaki K.
タイトル Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit.
ジャーナル Elife
Abstract The target of rapamycin (TOR) protein kinase forms multi-subunit TOR complex 1 (TORC1) and TOR complex 2 (TORC2), which exhibit distinct substrate specificities. Sin1 is one of the TORC2-specific subunit essential for phosphorylation and activation of certain AGC-family kinases. Here, we show that Sin1 is dispensable for the catalytic activity of TORC2, but its conserved region in the middle (Sin1CRIM) forms a discrete domain that specifically binds the TORC2 substrate kinases. Sin1CRIM fused to a different TORC2 subunit can recruit the TORC2 substrate Gad8 for phosphorylation even in the sin1 null mutant of fission yeast. The solution structure of Sin1CRIM shows a ubiquitin-like fold with a characteristic acidic loop, which is essential for interaction with the TORC2 substrates. The specific substrate-recognition function is conserved in human Sin1CRIM, which may represent a potential target for novel anticancer drugs that prevent activation of the mTORC2 substrates such as AKT.
巻・号 6
公開日 2017-3-7
DOI 10.7554/eLife.19594
PII e19594
PMID 28264193
PMC PMC5340527
MeSH Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Carrier Proteins / chemistry* Carrier Proteins / genetics Carrier Proteins / metabolism* Conserved Sequence HEK293 Cells Humans Magnetic Resonance Spectroscopy Mechanistic Target of Rapamycin Complex 2 / metabolism* Models, Molecular Protein Binding Protein Conformation Protein Folding Protein Interaction Mapping Schizosaccharomyces / enzymology Schizosaccharomyces pombe Proteins / chemistry* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Substrate Specificity
IF 7.08
リソース情報
酵母 FYC550(psk1)?
ヒト・動物細胞 MCF7(RCB1904) 293T(RCB2202)