School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
Biophys J. 2019 May 7;116(9):1586-1597. doi: 10.1016/j.bpj.2019.03.025. Epub 2019 Apr 2.
A docking procedure is described that allows the transmembrane surface of a G protein-coupled receptor (GPCR) to be swept rapidly for potential binding sites for cholesterol at the bilayer interfaces on the two sides of the membrane. The procedure matches 89% of the cholesterols resolved in published GPCR crystal structures, when cholesterols likely to be crystal packing artifacts are excluded. Docking poses are shown to form distinct clusters on the protein surface, the clusters corresponding to "greasy hollows" between protein ridges. Docking poses depend on the angle of tilt of the GPCR in the surrounding lipid bilayer. It is suggested that thermal motion could alter the optimal binding pose for a cholesterol molecule, with the range of binding poses within a cluster providing a guide to the range of thermal motions likely for a cholesterol within a binding site.
描述了一种对接程序，该程序允许 G 蛋白偶联受体 (GPCR) 的跨膜表面快速扫过膜两侧双层界面上胆固醇的潜在结合位点。当排除可能是晶体包装假象的胆固醇时，该程序匹配了已发表的 GPCR 晶体结构中解析出的 89%的胆固醇。对接构象在蛋白质表面上形成明显的簇，这些簇对应于蛋白质脊之间的“油腻凹坑”。对接构象取决于 GPCR 在周围脂质双层中的倾斜角度。有人建议，热运动会改变胆固醇分子的最佳结合构象，簇内的结合构象范围为胆固醇在结合位点内的热运动范围提供了指导。
