Hamburg Unit, European Molecular Biology Laboratory c/o DESY Hamburg, Germany.
Unit of Virus Host Cell Interactions, University Grenoble Alpes Grenoble, France ; Unit of Virus Host Cell Interactions, Centre National de la Recherche Scientifique Grenoble, France.
Front Mol Biosci. 2014 Oct 28;1:20. doi: 10.3389/fmolb.2014.00020. eCollection 2014.
Endophilin-A1 belongs to the family of BAR domain containing proteins that catalyze membrane remodeling processes via sensing, inducing and stabilizing membrane curvature. We show that the BAR domain of endophilin-A1 binds arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA into a defined structure. We studied low resolution structures of endophilin-A1-BAR and its complex with arachidonyl-CoA in solution using synchrotron small-angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be dimeric at lower concentrations but builds tetramers and higher order complexes with increasing concentrations. Extensive titration SAXS studies revealed that the BAR domain produces a homogenous complex with the lipid micelles. The structural model of the complexes revealed two arachidonyl-CoA micelles bound to the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the bound micelles significantly decreases compared to that of the free micelles, and this structural result may provide hints on the potential biological relevance of the endophilin-A1-BAR interaction with arachidonyl CoA.
内啡肽-A1 属于 BAR 结构域蛋白家族，通过感应、诱导和稳定膜曲率来催化膜重塑过程。我们表明，内啡肽-A1 的 BAR 结构域结合花生四烯酸，并将其辅酶 A（CoA）激活形式，花生四烯酰 CoA 塑造成特定的结构。我们使用同步辐射小角 X 射线散射（SAXS）在溶液中研究了内啡肽-A1-BAR 及其与花生四烯酰 CoA 复合物的低分辨率结构。较低浓度下，游离的内啡肽-A1-BAR 结构域显示为二聚体，但随着浓度的增加，会形成四聚体和更高阶的复合物。广泛的滴定 SAXS 研究表明，BAR 结构域与脂质胶束形成均匀的复合物。复合物的结构模型显示，两个花生四烯酰 CoA 胶束结合在内啡肽-A1-BAR 二聚体的远端臂上。有趣的是，与游离胶束相比，结合胶束的半径显著减小，这一结构结果可能为内啡肽-A1-BAR 与花生四烯酰 CoA 相互作用的潜在生物学意义提供线索。
