Principles of Alternating Access in Multidrug and Toxin Extrusion (MATE) Transporters.

Principles of Alternating Access in Multidrug and Toxin Extrusion (MATE) Transporters.
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DOI:
10.1016/j.jmb.2021.166959
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发表时间:
2021-08-06
影响因子:
5.6
通讯作者:
Mchaourab HS
Mchaourab HS
中科院分区:
生物学2区
文献类型:
--
作者:
Claxton DP;Jagessar KL;Mchaourab HS

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多药和毒素挤出(MATE)转运蛋白可催化多种化学和结构多样化的化合物(包括抗菌剂和化疗药物)的主动外流,从而促进病原菌和癌症的多药耐药性。人们采取了多种方法来研究 MATE 转运蛋白能量转导和底物易位的结构基础。代表所有三个 MATE 亚家族成员的晶体结构已在交替访问机制的背景下进行了解释,该机制假定在电化学离子梯度驱动的构象循环中占据不同的结构中间体。在这里,我们回顾了 MATE 转运蛋白的结构生物学,将晶体学模型与生物物理和计算研究相结合,以定义塑造运输能量景观的分子决定因素。这种整体分析强调了 MATE 家族中共享和不同的结构和功能特征,这些特征支撑了保守结构支架框架内机械多样性的新兴主题。
The multidrug and toxin extrusion (MATE) transporters catalyze active efflux of a broad range of chemically- and structurally-diverse compounds including antimicrobials and chemotherapeutics, thus contributing to multidrug resistance in pathogenic bacteria and cancers. Multiple methodological approaches have been taken to investigate the structural basis of energy transduction and substrate translocation in MATE transporters. Crystal structures representing members from all three MATE subfamilies have been interpreted within the context of an alternating access mechanism that postulates occupation of distinct structural intermediates in a conformational cycle powered by electrochemical ion gradients. Here we review the structural biology of MATE transporters, integrating the crystallographic models with biophysical and computational studies to define the molecular determinants that shape the transport energy landscape. This holistic analysis highlights both shared and disparate structural and functional features within the MATE family, which underpin an emerging theme of mechanistic diversity within the framework of a conserved structural scaffold.
DOI: 10.1073/pnas.1802417115
发表时间: 2018-07-03
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