Watanabe Yasunori, Tamura Yasushi, Kawano Shin, Endo Toshiya
1] Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto, 603-8555, Japan [2] JST/CREST, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto, 603-8555, Japan [3] JST/CREST, Research Center for Materials Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
1] JST/CREST, Research Center for Materials Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan [2] Research Center for Materials Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
Nat Commun. 2015 Aug 3;6:7922. doi: 10.1038/ncomms8922.
Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.
真核细胞被分隔成由膜包裹的细胞器,其功能依赖于脂质转运以实现脂质的膜特异性组成。在这里,我们聚焦于介导线粒体外膜与内膜之间磷脂酸(PA)转移的Ups1-Mdm35系统,并确定了结合和未结合PA的Mdm35以及Ups1-Mdm35的X射线结构。Ups1-Mdm35复合物构成一个具有深口袋和灵活Ω环盖子的单一结构域。基于结构的突变分析表明,口袋底部的一个碱性残基和Ω环盖子对于Ups1结合后从膜中提取PA很重要。Mdm35的解离增强了Ups1与膜的结合。我们还表明,口袋入口周围的碱性残基对于Ups1与膜的结合以及PA的提取很重要。这些结果为理解线粒体膜之间PA转移的机制提供了结构基础。