Miliara Xeni, Garnett James A, Tatsuta Takashi, Abid Ali Ferdos, Baldie Heather, Pérez-Dorado Inmaculada, Simpson Peter, Yague Ernesto, Langer Thomas, Matthews Stephen
Department of Life Sciences, Imperial College London, London, UK.
Department of Life Sciences, Imperial College London, London, UK School of Biological and Chemical Sciences, Joseph Priestley Building Queen Mary University of London, London, UK.
EMBO Rep. 2015 Jul;16(7):824-35. doi: 10.15252/embr.201540229. Epub 2015 Jun 12.
The composition of the mitochondrial membrane is important for its architecture and proper function. Mitochondria depend on a tightly regulated supply of phospholipid via intra-mitochondrial synthesis and by direct import from the endoplasmic reticulum. The Ups1/PRELI-like family together with its mitochondrial chaperones (TRIAP1/Mdm35) represent a unique heterodimeric lipid transfer system that is evolutionary conserved from yeast to man. Work presented here provides new atomic resolution insight into the function of a human member of this system. Crystal structures of free TRIAP1 and the TRIAP1-SLMO1 complex reveal how the PRELI domain is chaperoned during import into the intermembrane mitochondrial space. The structural resemblance of PRELI-like domain of SLMO1 with that of mammalian phoshatidylinositol transfer proteins (PITPs) suggest that they share similar lipid transfer mechanisms, in which access to a buried phospholipid-binding cavity is regulated by conformationally adaptable loops.
线粒体膜的组成对于其结构和正常功能至关重要。线粒体依赖通过线粒体内合成以及从内质网直接导入来严格调控磷脂的供应。Ups1/PRELI样家族及其线粒体伴侣蛋白（TRIAP1/Mdm35）代表了一种独特的异二聚体脂质转运系统，从酵母到人类在进化上保守。本文所展示的研究工作为该系统的一个人类成员的功能提供了新的原子分辨率见解。游离TRIAP1和TRIAP1-SLMO1复合物的晶体结构揭示了PRELI结构域在导入线粒体外膜间隙期间是如何被伴侣蛋白作用的。SLMO1的PRELI样结构域与哺乳动物磷脂酰肌醇转运蛋白（PITP）的结构相似性表明它们共享相似的脂质转运机制，其中对一个埋藏的磷脂结合腔的 access 通过构象适应性环来调控。 （注：这里“access”未准确翻译，结合语境可能是“接近、进入”等意思，因原文表述不太清晰暂保留英文）
