2RVK

Refined solution structure of Schizosaccharomyces pombe Sin1 CRIM domain

Summary for 2RVK

• Entry DOI: 10.2210/pdb2rvk/pdb
• Related: 2RUJ
• NMR Information: BMRB: 11546
• Descriptor: Stress-activated map kinase-interacting protein 1 (1 entity in total)
• Functional Keywords: sin1, crim domain, torc2, paramagnetic relaxation enhancement, cell cycle
• Biological source: Schizosaccharomyces pombe 972h- (Fission yeast)
• Total number of polymer chains: 1
• Total formula weight: 17590.61

Authors

Furuita, K.,Kataoka, S.,Shiozaki, K.,Kojima, C. (deposition date: 2015-12-10, release date: 2017-01-25, Last modification date: 2024-05-15)

Primary citation

Tatebe, H.,Murayama, S.,Yonekura, T.,Hatano, T.,Richter, D.,Furuya, T.,Kataoka, S.,Furuita, K.,Kojima, C.,Shiozaki, K.
Substrate specificity of TOR complex 2 is determined by a ubiquitin-fold domain of the Sin1 subunit.
Elife, 6:-, 2017

PubMed 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 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.

PubMed: 28264193
DOI: 10.7554/eLife.19594

Experimental method

SOLUTION NMR