Interrogating Membrane Protein Conformational Dynamics within Native Lipid Compositions

Interrogating Membrane Protein Conformational Dynamics within Native Lipid Compositions
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研究天然脂质组合物中的膜蛋白构象动力学

DOI:
10.1002/anie.201709657
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发表时间:
2017-12-04
影响因子:
16.6
通讯作者:
Booth, Paula J.
Booth, Paula J.
中科院分区:
化学1区
文献类型:
--
作者:
Reading, Eamonn;Hall, Zoe;Booth, Paula J.

文献摘要

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膜蛋白和膜脂之间的相互作用对细胞功能很重要,然而,能够在天然脂质环境中询问蛋白质动态的工具很少,而且往往是侵入性的。我们发现,苯乙烯-马来酸脂质颗粒(SMALP)技术可以与氢-氚交换质谱仪(HDX-MS)相结合来研究天然脂双层中膜蛋白的构象动力学。我们展示了在三种不同的天然脂组成中捕获的菱形蛋白酶GlpG的可及性和动力学的变化,并确定了对天然脂环境变化敏感的蛋白质区域。我们的结果说明了这一方法对于区分天然脂类成分在调节膜蛋白构象动力学中的假定作用(S)的价值。
The interplay between membrane proteins and the lipids of the membrane is important for cellular function, however, tools enabling the interrogation of protein dynamics within native lipid environments are scarce and often invasive. We show that the styrene-maleic acid lipid particle (SMALP) technology can be coupled with hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate membrane protein conformational dynamics within native lipid bilayers. We demonstrate changes in accessibility and dynamics of the rhomboid protease GlpG, captured within three different native lipid compositions, and identify protein regions sensitive to changes in the native lipid environment. Our results illuminate the value of this approach for distinguishing the putative role(s) of the native lipid composition in modulating membrane protein conformational dynamics.