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유전체 항상성 연구단
유전체 항상성 연구단
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Crystal structures of Mmm1 and Mdm12-Mmm1 reveal mechanistic insight into phospholipid trafficking at ER-mitochondria contact sites

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Title
Crystal structures of Mmm1 and Mdm12-Mmm1 reveal mechanistic insight into phospholipid trafficking at ER-mitochondria contact sites
Author(s)
Hanbin Jeong; Jumi Park; Youngsoo Jun; Changwook Lee
Publication Date
2017-11
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-PHYSICAL SCIENCES, v.114, no.45, pp.E9502 - E9511
Publisher
NATL ACAD SCIENCES
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 angstrom and 3.8 angstrom 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-angstrom-long continuous hydrophobic tunnel that facilitates phospholipid transport. The Mdm12-Mmm1 complex binds all glycerophospholipids except for phosphatidylethanolamine (PE) in vitro.
URI
http://pr.ibs.re.kr/handle/8788114/4149
DOI
10.1073/pnas.1715592114
ISSN
0027-8424
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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