Frost Adam, Perera Rushika, Roux Aurélien, Spasov Krasimir, Destaing Olivier, Egelman Edward H, De Camilli Pietro, Unger Vinzenz M
Departments of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510, USA.
Cell. 2008 Mar 7;132(5):807-17. doi: 10.1016/j.cell.2007.12.041.
BAR superfamily domains shape membranes through poorly understood mechanisms. We solved structures of F-BAR modules bound to flat and curved bilayers using electron (cryo)microscopy. We show that membrane tubules form when F-BARs polymerize into helical coats that are held together by lateral and tip-to-tip interactions. On gel-state membranes or after mutation of residues along the lateral interaction surface, F-BARs adsorb onto bilayers via surfaces other than their concave face. We conclude that membrane binding is separable from membrane bending, and that imposition of the module's concave surface forces fluid-phase bilayers to bend locally. Furthermore, exposure of the domain's lateral interaction surface through a change in orientation serves as the crucial trigger for assembly of the helical coat and propagation of bilayer bending. The geometric constraints and sequential assembly of the helical lattice explain how F-BAR and classical BAR domains segregate into distinct microdomains, and provide insight into the spatial regulation of membrane invagination.
BAR 超家族结构域通过尚不明确的机制塑造膜结构。我们利用电子（冷冻）显微镜解析了与扁平及弯曲双层膜结合的 F-BAR 模块的结构。我们发现，当 F-BAR 聚合成螺旋衣被时会形成膜小管，这些螺旋衣被通过侧向和尖端对尖端的相互作用聚集在一起。在凝胶态膜上或沿着侧向相互作用表面的残基发生突变后，F-BAR 通过其凹面以外的表面吸附到双层膜上。我们得出结论，膜结合与膜弯曲是可分离的，并且模块凹面的施加会迫使液相双层膜局部弯曲。此外，通过方向变化暴露结构域的侧向相互作用表面是螺旋衣被组装和双层膜弯曲传播的关键触发因素。螺旋晶格的几何约束和顺序组装解释了 F-BAR 和经典 BAR 结构域如何分离成不同的微结构域，并为膜内陷的空间调控提供了见解。
