title: Structural basis of intramitochondrial phosphatidic acid transport mediated by Ups1-Mdm35 complex.
abstract: Ups1 forms a complex with Mdm35 and is critical for the transport of phosphatidic acid (PA) from the mitochondrial outer membrane to the inner membrane. We report the crystal structure of the Ups1-Mdm35-PA complex and the functional characterization of Ups1-Mdm35 in PA binding and transfer. Ups1 features a barrel-like structure consisting of an antiparallel β-sheet and three α-helices. Mdm35 adopts a three-helical clamp-like structure to wrap around Ups1 to form a stable complex. The β-sheet and α-helices of Ups1 form a long tunnel-like pocket to accommodate the substrate PA, and a short helix α2 acts as a lid to cover the pocket. The hydrophobic residues lining the pocket and helix α2 are critical for PA binding and transfer. In addition, a hydrophilic patch on the surface of Ups1 near the PA phosphate-binding site also plays an important role in the function of Ups1-Mdm35. Our study reveals the molecular basis of the function of Ups1-Mdm35 and sheds new light on the mechanism of intramitochondrial phospholipid transport by the MSF1/PRELI family proteins.
authors.affiliation: National Center for Protein Science Shanghai and State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: He
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yao
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: National Center for Protein Science Shanghai and State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jianchuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jianxu
authors.initials: J
authors.lastname: Li
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qi
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China hwxue@sibs.ac.cn jpding@sibcb.ac.cn pengzhang01@sibs.ac.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xue
authors.affiliation: National Center for Protein Science Shanghai and State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China hwxue@sibs.ac.cn jpding@sibcb.ac.cn pengzhang01@sibs.ac.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Ding
authors.affiliation: National Key Laboratory of Plant Molecular Genetics, Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China hwxue@sibs.ac.cn jpding@sibcb.ac.cn pengzhang01@sibs.ac.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D002308:Cardiolipins / Q000096:biosynthesis; D018360:Crystallography, X-Ray; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D010712:Phosphatidic Acids / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; C552370:Mdm35 protein, S cerevisiae; D024101:Mitochondrial Proteins; D010712:Phosphatidic Acids; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; C512497:Ups1 protein, S cerevisiae
keywords: cardiolipin synthesis; lipid transfer protein; mitochondrial morphology; phosphatidic acid transport