Structural and functional analyses of Mmm1 and Mdm12 in the ERMES complex

2015 Fiscal Year Final Research Report

• Project/Area Number: 25840020
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kyoto Sangyo University (2014-2015); Nagoya University (2013)
• Principal Investigator: KAWANO Shin 京都産業大学, 総合生命科学部, 研究助教 (90431676)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 結晶構造 / オルガネラネットワーク / リン脂質

Outline of Final Research Achievements

The ERMES complex was recently found to be involved in the tethering system between ER and mitochondria in yeast. The complex consists of four core components (Mmm1, Mmm2, Mdm10, and Mdm12) and is supposed as a transducer of phospholipids between those two organelle. In this study, we succeeded in determining the crystal structure of Mdm12. In addition, the functional analyses of Mdm12 and Mdm12-Mmm1 soluble domain complex were also performed.
The crystal structure of Mdm12 belongs to SMP domain fold, which can accommodate a phospholipid in its cave structure. Furthermore, in vitro lipid transfer assay using Mdm12 and Mdm12-Mmm1 complex showed that the lipid transfer activity of Mdm12 was largely enhanced by forming a hetero oligomeric complex with Mmm1. These observations indicate that ERMES complex transfers phospholipids between the ER and mitochondrial outer membrane via Mdm12-Mmm1 complex as a minimal unit.

Free Research Field

構造生物学