School of Biological Sciences, University of Southampton, Southampton, United Kingdom.
Biophys J. 2019 Nov 19;117(10):2020-2033. doi: 10.1016/j.bpj.2019.10.011. Epub 2019 Oct 18.
Transient receptor potential (TRP) channels are members of a large family of ion channels located in membranes rich in cholesterol, some of whose functions are affected by the cholesterol content of the membrane. Here, cholesterol binding to TRPs is studied using a docking procedure that allows the transmembrane surface of a TRP to be swept rapidly for potential binding sites at the interfaces on the two sides of the membrane. Cholesterol docking poses determined in this way match 89% of the cholesterol hemisuccinate molecules in published TRP structures when cholesterol hemisuccinate molecules unlikely to represent typical bound cholesterols are excluded. TRPs are tetrameric, with large clefts at the interfaces between subunits; cholesterol poses are located in hollows, largely within these clefts. Comparison of cholesterol poses with phospholipid binding sites suggests that binding of cholesterol to a TRP need not result in displacement of phospholipid molecules from the TRP surface.
瞬时受体电位 (TRP) 通道是位于富含胆固醇的膜中的一大类离子通道成员，其某些功能受膜中胆固醇含量的影响。在这里，使用对接程序研究了胆固醇与 TRP 的结合，该程序允许快速扫描 TRP 的跨膜表面，以寻找膜两侧界面上的潜在结合位点。当排除不太可能代表典型结合胆固醇的胆固醇半琥珀酸分子时，以这种方式确定的胆固醇对接构象与已发表的 TRP 结构中的 89%的胆固醇半琥珀酸分子匹配。TRP 是四聚体，在亚基之间的界面处有大的裂隙；胆固醇构象位于凹陷处，主要在这些裂隙内。将胆固醇构象与磷脂结合位点进行比较表明，胆固醇与 TRP 的结合不一定导致磷脂分子从 TRP 表面移位。
