The structures of mitochondrial transporters and uncoupling proteins are 3-fold pseudosymmetrical, but their substrates and coupling ions are not. Thus, deviations from symmetry are to be expected in the substrate and ion-binding sites in the central aqueous cavity. By analyzing the 3-fold pseudosymmetrical repeats from which their sequences are made, conserved asymmetric residues were found to cluster in a region of the central cavity identified previously as the common substrate-binding site. Conserved symmetrical residues required for the transport mechanism were found at the water–membrane interfaces, and they include the three PX[DE]XX[RK] motifs, which form a salt bridge network on the matrix side of the cavity when the substrate-binding site is open to the mitochondrial intermembrane space. Symmetrical residues in three [FY][DE]XX[RK] motifs are on the cytoplasmic side of the cavity and could form a salt bridge network when the substrate-binding site is accessible from the mitochondrial matrix. It is proposed that the opening and closing of the carrier may be coupled to the disruption and formation of the 2 salt bridge networks via a 3-fold rotary twist induced by substrate binding. The interaction energies of the networks allow members of the transporter family to be classified as strict exchangers or uniporters.
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机译：线粒体转运蛋白和解偶联蛋白的结构是3倍假对称的，但它们的底物和偶联离子却不是。因此，在基底和中央含水腔中的离子结合位点中，可以预期不对称。通过分析3倍假对称重复序列（由其序列组成），发现保守的不对称残基聚集在中央空腔的区域中，该区域先前被确定为常见的底物结合位点。在水-膜界面发现了运输机制所需的保守对称残基，它们包括三个PX [DE] XX [RK]基序，当底物结合时，它们在空腔的基质侧形成盐桥网络该部位向线粒体膜间空间开放。三个[FY] [DE] XX [RK]基序中的对称残基位于空腔的细胞质侧，当可以从线粒体基质接近底物结合位点时，它们可能形成盐桥网络。提出载体的打开和闭合可以通过由底物结合引起的3倍旋转扭曲与2个盐桥网络的破坏和形成偶联。网络的相互作用能使运输族的成员被分类为严格的交换者或单向者。
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