Department of Chemistry, Hillsdale College, Hillsdale, MI 49242, United States.
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, United States.
Curr Opin Struct Biol. 2017 Aug;45:100-108. doi: 10.1016/j.sbi.2016.12.006. Epub 2016 Dec 30.
Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na-coupled amino acid transporter LeuT and the Na-coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective.
次级主动转运体将底物的 uphill 转运与电化学离子梯度偶联。转运体构象运动，通常称为交替访问，使中央配体结合位点相对于膜改变其取向。在这里，我们回顾了交替访问的主题，并探讨了离子梯度能量的转导如何为 LeuT 折叠类转运体中的这个过程提供动力，其中晶体学、计算和光谱学方法的结合已经产生了运输循环的详细模型。具体来说，我们比较了 Na 偶联氨基酸转运体 LeuT 和 Na 偶联海因酶转运体 Mhp1 的发现。尽管这些研究阐明了转运体结构和动力学的多个方面，但仍有一些悬而未决的问题，迄今为止阻碍了从能量景观的角度理解转运机制。
