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线粒体载体运输的结构机制。

Structural Mechanism of Transport of Mitochondrial Carriers.

机构信息

Medical Research Council Mitochondrial Biology Unit, Keith Peters Building, University of Cambridge, Cambridge CB2 0XY, United Kingdom; email:

出版信息

Annu Rev Biochem. 2021 Jun 20;90:535-558. doi: 10.1146/annurev-biochem-072820-020508. Epub 2021 Feb 8.

DOI:10.1146/annurev-biochem-072820-020508
PMID:33556281
Abstract

Members of the mitochondrial carrier family [solute carrier family 25 (SLC25)] transport nucleotides, amino acids, carboxylic acids, fatty acids, inorganic ions, and vitamins across the mitochondrial inner membrane. They are important for many cellular processes, such as oxidative phosphorylation of lipids and sugars, amino acid metabolism, macromolecular synthesis, ion homeostasis, cellular regulation, and differentiation. Here, we describe the functional elements of the transport mechanism of mitochondrial carriers, consisting of one central substrate-binding site and two gates with salt-bridge networks on either side of the carrier. Binding of the substrate during import causes three gate elements to rotate inward, forming the cytoplasmic network and closing access to the substrate-binding site from the intermembrane space. Simultaneously, three core elements rock outward, disrupting the matrix network and opening the substrate-binding site to the matrix side of the membrane. During export, substrate binding triggers conformational changes involving the same elements but operating in reverse.

摘要

线粒体载体家族(溶质载体家族 25(SLC25))的成员将核苷酸、氨基酸、羧酸、脂肪酸、无机离子和维生素跨线粒体内膜运输。它们对于许多细胞过程很重要,例如脂质和糖的氧化磷酸化、氨基酸代谢、大分子合成、离子平衡、细胞调节和分化。在这里,我们描述了线粒体载体运输机制的功能要素,它由一个中央底物结合位点和两个带有盐桥网络的门组成,载体位于门的两侧。在导入过程中,底物的结合导致三个门元件向内旋转,形成细胞质网络,并从膜间空间关闭进入底物结合位点的通道。同时,三个核心元件向外摆动,破坏基质网络并打开基质侧的底物结合位点。在输出过程中,底物结合触发涉及相同元件的构象变化,但以相反的方式运作。

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