Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes
Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes
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DOI：
10.1016/j.sbi.2016.12.006
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发表时间：
2017-08-01
影响因子：
6.8
通讯作者：
Mchaourab, Hassane S.
中科院分区：
文献类型：
--
作者：
Kazmier, Kelli;Claxton, Derek P.;Mchaourab, Hassane S.
次级活性转运体将底物的上行转运与电化学离子梯度相结合。转运蛋白构象运动，通常被称为交替访问，使中心配体结合位置相对于膜改变其方向。在这里，我们审查了交替访问和离子梯度能量的转换为这一过程提供动力的Leut-Fold类转运体的主题，在这些转运体中，结晶学、计算和光谱方法已经收敛，以产生详细的运输周期模型。具体地说，我们比较了Na+偶联的氨基酸转运蛋白Leut和Ne偶联的海因转运蛋白Mhpl的结果。虽然这些研究已经阐明了转运体结构和动力学的多个方面，但到目前为止，仍有一些问题尚未解决，这些问题阻碍了从能源景观的角度理解转运体的机制。
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 Ne-coupled hydantoin transporter Mhpl. 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.