5YK7

Crystal Structure of Mdm12-Mmm1 complex

5YK7 の概要

• エントリーDOI: 10.2210/pdb5yk7/pdb
• 分子名称: Maintenance of mitochondrial morphology protein 1, Mitochondrial distribution and morphology protein 12, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: mmm1, mdm12, ermes, phospholipid, membrane contact site, lipid transport
• 由来する生物種: Zygosaccharomyces rouxii (strain ATCC 2623 / CBS 732 / NBRC 1130 / NCYC 568 / NRRL Y-229) (Candida mogii); 詳細
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass type I membrane protein : C5DRQ1; Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side: Q92328
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 106711.72

構造登録者

Jeong, H.,Park, J.,Lee, C. (登録日: 2017-10-12, 公開日: 2018-01-10, 最終更新日: 2023-11-22)

主引用文献

Jeong, H.,Park, J.,Jun, Y.,Lee, C.
Crystal structures of Mmm1 and Mdm12-Mmm1 reveal mechanistic insight into phospholipid trafficking at ER-mitochondria contact sites.
Proc. Natl. Acad. Sci. U.S.A., 114:E9502-E9511, 2017

PubMed Abstract: The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) comprises mitochondrial distribution and morphology 12 (Mdm12), maintenance of mitochondrial morphology 1 (Mmm1), Mdm34, and Mdm10 and mediates physical membrane contact sites and nonvesicular lipid trafficking between the ER and mitochondria in yeast. Herein, we report two crystal structures of the synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain of Mmm1 and the Mdm12-Mmm1 complex at 2.8 Å and 3.8 Å resolution, respectively. Mmm1 adopts a dimeric SMP structure augmented with two extra structural elements at the N and C termini that are involved in tight self-association and phospholipid coordination. Mmm1 binds two phospholipids inside the hydrophobic cavity, and the phosphate ion of the distal phospholipid is specifically recognized through extensive H-bonds. A positively charged concave surface on the SMP domain not only mediates ER membrane docking but also results in preferential binding to glycerophospholipids such as phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylglycerol (PG), and phosphatidylserine (PS), some of which are substrates for lipid-modifying enzymes in mitochondria. The Mdm12-Mmm1 structure reveals two Mdm12s binding to the SMP domains of the Mmm1 dimer in a pairwise head-to-tail manner. Direct association of Mmm1 and Mdm12 generates a 210-Å-long continuous hydrophobic tunnel that facilitates phospholipid transport. The Mdm12-Mmm1 complex binds all glycerophospholipids except for phosphatidylethanolamine (PE) in vitro.

PubMed: 29078410
DOI: 10.1073/pnas.1715592114

実験手法

X-RAY DIFFRACTION (3.799 Å)