Probing the dynamic regulation of peripheral membrane proteins using hydrogen deuterium exchange-MS (HDX-MS)
Probing the dynamic regulation of peripheral membrane proteins using hydrogen deuterium exchange-MS (HDX-MS)
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DOI：
10.1042/bst20150065
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发表时间：
2015-10-01
影响因子：
3.9
通讯作者：
Burke, John E.
中科院分区：
文献类型：
--
作者：
Vadas, Oscar;Burke, John E.
许多细胞信号事件是由蛋白复合物选择性募集到膜上控制的。由于难以在模拟天然生物膜环境的条件下工作，确定脂质信号复合物如何在特定膜室上募集、组装和调节的分子基础仍然具有挑战性。酶在膜上的募集受到多种调节机制的控制，包括与特定脂质的结合、蛋白质-蛋白质相互作用、膜曲率以及翻译后修饰。氢氘交换质谱（HDX-MS）是研究膜信号酶和复合物调控的有力工具，该技术允许对膜结合和招募时的蛋白质动力学进行询问。本文将重点介绍HDX-MS的理论和发展，以及HDX-MS在研究脂质信号酶的分子基础，特别是磷酸肌肽3激酶（PI3Ks）的调控和激活方面的应用。
Many cellular signalling events are controlled by the selective recruitment of protein complexes to membranes. Determining the molecular basis for how lipid signalling complexes are recruited, assembled and regulated on specific membrane compartments has remained challenging due to the difficulty of working in conditions mimicking native biological membrane environments. Enzyme recruitment to membranes is controlled by a variety of regulatory mechanisms, including binding to specific lipid species, protein-protein interactions, membrane curvature, as well as post-translational modifications. A powerful tool to study the regulation of membrane signalling enzymes and complexes is hydrogen deuterium exchange-MS (HDX-MS), a technique that allows for the interrogation of protein dynamics upon membrane binding and recruitment. This review will highlight the theory and development of HDX-MS and its application to examine the molecular basis of lipid signalling enzymes, specifically the regulation and activation of phosphoinositide 3-kinases (PI3Ks).