Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit.
Elife
; 62017 03 07.
Article
in En
| MEDLINE
| ID: mdl-28264193
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carrier Proteins
/
Schizosaccharomyces pombe Proteins
/
Mechanistic Target of Rapamycin Complex 2
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Elife
Year:
2017
Document type:
Article
Affiliation country:
Japan