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Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit
- Source :
- eLife, Vol 6 (2017)
- Publication Year :
- 2017
- Publisher :
- eLife Sciences Publications Ltd, 2017.
-
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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2c6864ba6df44826bced7e53c0746a6c
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.19594