Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside
Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside
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DOI：
10.1038/nature02056
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发表时间：
2003-11-06
期刊：
影响因子：
64.8
通讯作者：
Brandolin, R
中科院分区：
文献类型：
--
作者：
Pebay-Peyroula, E;Dahout-Gonzalez, C;Brandolin, R
ATP是细胞的主要能量货币，通过水解成ADP和无机磷酸盐为细胞质中的大多数生物合成反应提供燃料。由于ATP的再合成发生在线粒体基质中，ATP被输出到细胞质中，而ADP被输入到基质中。交换是由一个单一的蛋白质，ADP/ATP载体。在这里，我们已经解决了牛载体结构的分辨率为2.2埃的X射线晶体学与抑制剂，羧基糖苷复合。六个α-螺旋形成一个紧凑的跨膜结构域，其在表面朝向线粒体内外膜之间的空间，揭示了一个深深的凹陷。在其底部，定位了携带核苷酸载体（RRRMMM）的签名的六肽。我们的结构，再加上早期的生化结果，表明运输基板绑定到底部的腔和易位的结果从一个短暂的过渡从一个“坑”到一个“通道”的构象。
ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved the bovine carrier structure at a resolution of 2.2 Angstrom by X-ray crystallography in complex with an inhibitor, carboxyatractyloside. Six alpha-helices form a compact transmembrane domain, which, at the surface towards the space between inner and outer mitochondrial membranes, reveals a deep depression. At its bottom, a hexapeptide carrying the signature of nucleotide carriers ( RRRMMM) is located. Our structure, together with earlier biochemical results, suggests that transport substrates bind to the bottom of the cavity and that translocation results from a transient transition from a 'pit' to a 'channel' conformation.