2017年3月
Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit
ELIFE
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- 巻
- 6
- 号
- 開始ページ
- e19594
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.7554/eLife.19594
- 出版者・発行元
- ELIFE SCIENCES PUBLICATIONS LTD
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.
- リンク情報
- ID情報
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- DOI : 10.7554/eLife.19594
- ISSN : 2050-084X
- Web of Science ID : WOS:000396110700001