Native Mass Spectrometry of Membrane Proteins.
Native Mass Spectrometry of Membrane Proteins.
复制标题
膜蛋白的天然质谱法。
DOI：
10.1021/acs.analchem.0c04342
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发表时间：
2021-01-12
影响因子：
7.4
通讯作者：
Marty MT
中科院分区：
文献类型：
--
作者：
Keener JE;Zhang G;Marty MT
由两亲性脂质双层形成的生物膜提供化学屏障以将细胞与其外部环境分离并限定亚细胞区室。包埋在这些脂质膜中的膜蛋白约占蛋白质组的30%，1，2，它们在细胞过程中发挥关键作用，如化学转运，信号转导和酶催化。由于这些重要作用，膜蛋白约占所有药物靶标的一半。3膜蛋白结构的表征是阐明其生化机制和开发新治疗方法的基础。然而，在蛋白质数据库（PDB）中，膜蛋白仅占高分辨率结构的2 - 3%。这些统计数据反映了一个显着的差距，在分析工具来表征膜蛋白的结构，功能和相互作用，特别是在脂质双层的背景下。在研究膜蛋白时有几个分析挑战。首先，膜蛋白的天然丰度通常较低，并且以高产率过表达和纯化膜蛋白可能具有挑战性。4 - 7因此，我们需要灵敏的分析方法，只需要少量的样品。其次，膜环境是高度异质性和不溶性的，许多技术不能在其自然环境中研究膜蛋白。最后，大多数分析方法需要溶解膜蛋白，但用于溶解的去污剂会使膜蛋白不稳定，并破坏关键的蛋白质-脂质相互作用。8 - 11换句话说，由于膜蛋白的两亲性，它们比可溶性蛋白具有更复杂的相互作用和环境约束。
Biological membranes formed of amphipathic lipid bilayers provide chemical barriers to separate cells from their external environments and define subcellular compartments. Membrane proteins embedded within these lipid membranes constitute about 30% of the proteome, 1, 2 and they play key roles in cellular processes such as chemical transport, signal transduction, and enzymatic catalysis. Due to these important roles, membrane proteins represent roughly half of all drug targets. 3Characterizing membrane protein structures is fundamental in elucidating their biochemical mechanisms and developing new therapeutics. However, membrane proteins represent only 2− 3% of high-resolution structures in the Protein Data Bank (PDB). These statistics reflect a significant gap in analytical tools to characterize membrane protein structure, function, and interactions, especially in the context of lipid bilayers. There are several analytical challenges in studying membrane proteins. First, the natural abundance of membrane proteins is typically low, and it can be challenging to overexpress and purify membrane proteins in high yields. 4− 7 Thus, we need sensitive analytical methods that only require small amounts of sample. Second, the membrane environment is highly heterogeneous and insoluble, and many techniques are not capable of studying membrane proteins in their natural context. Finally, most analytical methods require membrane proteins to be solubilized, but detergents used for solubilization can destabilize membrane proteins and disrupt key protein− lipid interactions. 8− 11 In other words, membrane proteins have more complex interactions and environmental constraints than soluble proteins due to their amphipathic nature.
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DOI：
10.1002/anie.201704849
发表时间：
2017-11-13
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Ambrose S;Housden NG;Gupta K;Fan J;White P;Yen HY;Marcoux J;Kleanthous C;Hopper JTS;Robinson CV
通讯作者：
Robinson CV
影响因子：
16.6
作者：
Cong X;Liu Y;Liu W;Liang X;Laganowsky A
通讯作者：
Laganowsky A
影响因子：
7.4
作者：
Benesch, JLP;Sobott, F;Robinson, CV
通讯作者：
Robinson, CV
影响因子：
15
作者：
Cong, Xiao;Liu, Yang;Laganowsky, Arthur
通讯作者：
Laganowsky, Arthur
影响因子：
5.4
作者：
Almen, Markus Sallman;Nordstrom, Karl J. V.;Schioth, Helgi B.
通讯作者：
Schioth, Helgi B.