Hydrogen/deuterium exchange-mass spectrometry of integral membrane proteins in native-like environments: current scenario and the way forward.
Hydrogen/deuterium exchange-mass spectrometry of integral membrane proteins in native-like environments: current scenario and the way forward.
复制标题
在类似天然的环境中积分膜蛋白的氢/氘交换质量光谱法：当前情况和前进方向。
DOI：
10.1042/ebc20220173
复制
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：
--
作者：
整合膜蛋白（IMP）执行一系列不同的功能，它们的功能障碍是许多病理条件的基础。因此，IMP构成了大多数药物靶标，并且阐明其作用机制已成为一个激烈的研究领域。从历史上看，IMP研究依赖于使用去污剂从膜中提取，这可能会扰乱其结构和动力学。为了解决这个问题，已经开发了一系列膜模拟物，其目的是将IMP重组到更准确地代表生物膜的天然样脂质环境中。氢/氘交换质谱（HDX-MS）已成为探测溶液中蛋白质动力学的通用工具。HDX-MS方法的持续发展使从业者能够使用越来越天然的膜模拟物研究IMP，甚至将IMP的研究推向体内细胞环境。因此，HDX-MS已经成熟，并在IMP结构生物学家工具包中发挥着越来越重要的作用。在目前的小型审查中，我们讨论了膜模拟物在HDX-MS背景下的演变，重点是开创性的出版物和最近的创新，导致了这一点。我们还讨论了最先进的方法和仪器的进步，这些进步可能在未来生成高质量的IMP HDX-MS数据中发挥重要作用。
Integral membrane proteins (IMPs) perform a range of diverse functions and their dysfunction underlies numerous pathological conditions. Consequently, IMPs constitute most drug targets, and the elucidation of their mechanism of action has become an intense field of research. Historically, IMP studies have relied on their extraction from membranes using detergents, which have the potential to perturbate their structure and dynamics. To circumnavigate this issue, an array of membrane mimetics has been developed that aim to reconstitute IMPs into native-like lipid environments that more accurately represent the biological membrane. Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has emerged as a versatile tool for probing protein dynamics in solution. The continued development of HDX-MS methodology has allowed practitioners to investigate IMPs using increasingly native-like membrane mimetics, and even pushing the study of IMPs into the in vivo cellular environment. Consequently, HDX-MS has come of age and is playing an ever-increasingly important role in the IMP structural biologist toolkit. In the present mini-review, we discuss the evolution of membrane mimetics in the HDX-MS context, focusing on seminal publications and recent innovations that have led to this point. We also discuss state-of-the-art methodological and instrumental advancements that are likely to play a significant role in the generation of high-quality HDX-MS data of IMPs in the future.
影响因子：
4.2
作者：
Zampieri V;Hilpert C;Garnier M;Gestin Y;Delolme S;Martin J;Falson P;Launay G;Chaptal V
通讯作者：
Chaptal V
影响因子：
3.9
作者：
Diller, Anna;Loudet, Cecile;Aussenac, Fabien;Raffard, Gerard;Fournier, Sylvie;Laguerre, Michel;Grelard, Axelle;Opella, Stanley J.;Marassi, Francesca M.;Dufourc, Erick J.
通讯作者：
Dufourc, Erick J.