The mechanism of transport by mitochondrial carriers based on analysis of symmetry
The mechanism of transport by mitochondrial carriers based on analysis of symmetry
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DOI：
10.1073/pnas.0809580105
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发表时间：
2008-11-18
影响因子：
11.1
通讯作者：
Kunji, Edmund R. S.
中科院分区：
文献类型：
--
作者：
Robinson, Alan J.;Overy, Catherine;Kunji, Edmund R. S.
线粒体转运体和解偶联蛋白的结构是3倍赝对称的，但它们的底物和偶联离子不是。因此，在基底和中央水腔中的离子结合位点中，对称性的偏差是可以预料的。通过分析构成其序列的3倍伪对称重复序列，发现保守的不对称残基聚集在先前确定为共同底物结合位点的中心空腔区域。在水膜界面处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，当底物结合位点向线粒体膜间空间开放时，它们在腔的基质侧形成盐桥网络。三个[FY][DE]XX[RK]基序中的对称残基位于空腔的细胞质侧，当底物结合位点可以从线粒体基质中到达时，可以形成盐桥网络。本文提出，载体的打开和关闭可能与底物结合引起的3倍旋转扭转引起的2个盐桥网络的破坏和形成相耦合。网络的相互作用能允许转运体家族的成员被分类为严格的交换体或单转运体。
The structures of mitochondrial transporters and uncoupling proteins are 3-fold pseuclosymmetrical, 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 pseuclosymmetrical 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.