Structural mass spectrometry approaches to understand multidrug efflux systems.
Structural mass spectrometry approaches to understand multidrug efflux systems.
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DOI：
10.1042/ebc20220190
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发表时间：
2023-03-29
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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作者：
多药外排泵在真核生物和原核生物中普遍存在，并在抗菌和多药耐药中具有重要意义。它们存在于细胞膜内，由于其疏水性和与组成复杂的脂质环境的关系，已被证明难以研究。结构质谱（MS）技术的进步使得研究这些系统以阐明其结构-功能关系的关键信息成为可能。例如，质谱技术可以报告蛋白质结构动力学、化学计量学、连通性、溶剂可及性以及与配体、脂质和其他蛋白质的结合相互作用。当与互补的结构生物学方法和分子动力学（MD）模拟结合使用时，这些信息证明是强大的。在本综述中，针对那些不熟悉质谱技术的人，我们报告了目前质谱在研究多药物外排系统中的应用，需要考虑的实际问题以及该领域的未来方向。在第一部分中，我们强调了研究多药物外排蛋白的重要性，并介绍了一系列不同的质谱技术，并解释了它们产生的信息。在第二部分中，我们回顾了最近利用质谱技术研究和描述一系列不同的多药物外排系统的研究。
Multidrug efflux pumps are ubiquitous across both eukaryotes and prokaryotes, and have major implications in antimicrobial and multidrug resistance. They reside within cellular membranes and have proven difficult to study owing to their hydrophobic character and relationship with their compositionally complex lipid environment. Advances in structural mass spectrometry (MS) techniques have made it possible to study these systems to elucidate critical information on their structure–function relationships. For example, MS techniques can report on protein structural dynamics, stoichiometry, connectivity, solvent accessibility, and binding interactions with ligands, lipids, and other proteins. This information proving powerful when used in conjunction with complementary structural biology methods and molecular dynamics (MD) simulations. In the present review, aimed at those not experts in MS techniques, we report on the current uses of MS in studying multidrug efflux systems, practical considerations to consider, and the future direction of the field. In the first section, we highlight the importance of studying multidrug efflux proteins, and introduce a range of different MS techniques and explain what information they yield. In the second section, we review recent studies that have utilised MS techniques to study and characterise a range of different multidrug efflux systems.
影响因子：
7.4
作者：
Leney, Aneika C.;McMorran, Lindsay M.;Radford, Sheena E.;Ashcroft, Alison E.
通讯作者：
Ashcroft, Alison E.