5YK6

Crystal Structure of Mmm1

Summary for 5YK6

• Entry DOI: 10.2210/pdb5yk6/pdb
• Descriptor: Maintenance of mitochondrial morphology protein 1, 1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE (3 entities in total)
• Functional Keywords: ermes, phospholipid, membrane contact site, lipid transport
• Biological source: Zygosaccharomyces rouxii (strain ATCC 2623 / CBS 732 / NBRC 1130 / NCYC 568 / NRRL Y-229) (Candida mogii)
• Cellular location: Endoplasmic reticulum membrane ; Single-pass type I membrane protein : C5DRQ1
• Total number of polymer chains: 1
• Total formula weight: 30993.34

Authors

Jeong, H.,Park, J.,Lee, C. (deposition date: 2017-10-12, release date: 2018-01-10, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)