Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK.
Angew Chem Int Ed Engl. 2017 Dec 4;56(49):15654-15657. doi: 10.1002/anie.201709657. Epub 2017 Nov 8.
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.
膜蛋白与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检测蛋白质动态的工具却很少，且通常具有侵入性。我们表明，苯乙烯-马来酸脂粒（SMALP）技术可以与氢氘交换质谱（HDX-MS）相结合，用于研究天然脂质双层中膜蛋白构象动力学。我们证明了菱形蛋白酶 GlpG 在三种不同天然脂质组成中的可及性和动力学变化，并鉴定出对天然脂质环境变化敏感的蛋白质区域。我们的结果阐明了这种方法的价值，可用于区分天然脂质组成在调节膜蛋白构象动力学中的潜在作用。
