Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS).
Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS).
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DOI：
10.1021/acs.chemrev.0c00983
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发表时间：
2021-05-12
期刊：
影响因子：
62.1
通讯作者：
Tanabe M
中科院分区：
文献类型：
--
作者：
Drew D;North RA;Nagarathinam K;Tanabe M
主要促进剂超家族(MFS)是已知最大的次级活性转运蛋白超家族。MFS转运体负责利用电化学梯度中储存的能量向下或上行运输广泛的底物。在过去的10年里，100多种不同的MFS转运蛋白结构覆盖了近40个成员，为拼接其运输周期的分子基础提供了一个原子框架。在这里，我们总结了MFS成员在底物识别和质子耦合方面的显著混杂，以及在实现底物转移过程中经历的复杂的门控机制。我们概述了一些研究，表明远离底物结合位点的残基对于微调底物识别和特异性的重要性与那些直接与底物配位的残基一样重要，以及一些MFS转运蛋白是如何进化成具有伴侣和信号功能的独特复合体的。通过对葡萄糖(GLUT)转运体和多药耐药(MDR)反向转运体的更深入的机制描述，我们概述了摇杆开关交替访问模型的新改进，例如质子偶联单糖运输的锁存机制。我们强调，对转运的充分理解需要阐明MFS转运体的动力学、能量格局，并确定脂质是如何调节速率转换的。
The major facilitator superfamily (MFS) is the largest known superfamily of secondary active transporters. MFS transporters are responsible for transporting a broad spectrum of substrates, either down their concentration gradient or uphill using the energy stored in the electrochemical gradients. Over the last 10 years, more than a hundred different MFS transporter structures covering close to 40 members have provided an atomic framework for piecing together the molecular basis of their transport cycles. Here, we summarize the remarkable promiscuity of MFS members in terms of substrate recognition and proton coupling as well as the intricate gating mechanisms undergone in achieving substrate translocation. We outline studies that show how residues far from the substrate binding site can be just as important for fine-tuning substrate recognition and specificity as those residues directly coordinating the substrate, and how a number of MFS transporters have evolved to form unique complexes with chaperone and signaling functions. Through a deeper mechanistic description of glucose (GLUT) transporters and multidrug resistance (MDR) antiporters, we outline novel refinements to the rocker-switch alternating-access model, such as a latch mechanism for proton-coupled monosaccharide transport. We emphasize that a full understanding of transport requires an elucidation of MFS transporter dynamics, energy landscapes, and the determination of how rate transitions are modulated by lipids.
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