Membrane remodeling is a common theme in a variety of cellular processes. Here, we investigated membrane remodeling N-BAR protein endophilin B1, a critical player in diverse intracellular trafficking events, including mitochondrial and Golgi fission, and apoptosis. We find that endophilin B1 assembles into helical scaffolds on membranes, and that both membrane binding and assembly are driven by interactions between N-terminal helix H0 and the lipid bilayer. Furthermore, we find that endophilin B1 membrane remodeling is auto-inhibited and identify direct SH3 domain-H0 interactions as the underlying mechanism. Our results indicate that lipid composition plays a role in dictating endophilin B1 activity. Taken together, this study provides insight into a poorly understood N-BAR protein family member and highlights molecular mechanisms that may be general for the regulation of membrane remodeling. Our work suggests that interplay between membrane lipids and membrane interacting proteins facilitates spatial and temporal coordination of membrane remodeling.

膜重塑是各种细胞过程中的一个共同主题。在这里，我们研究了膜重塑 N-BAR 蛋白内亲蛋白 B1，这是多种细胞内运输事件的关键参与者，包括线粒体和高尔基体裂变以及细胞凋亡。我们发现亲内蛋白 B1 在膜上组装成螺旋支架，并且膜结合和组装都是由 N 端螺旋 H0 和脂质双层之间的相互作用驱动的。此外，我们发现内皮素 B1 膜重塑是自动抑制的，并将直接的 SH3 域-H0 相互作用确定为潜在机制。我们的结果表明脂质成分在决定内皮素 B1 活性中起作用。综合起来，这项研究提供了对一个知之甚少的 N-BAR 蛋白家族成员的深入了解，并强调了可能普遍用于调节膜重塑的分子机制。我们的工作表明，膜脂和膜相互作用蛋白之间的相互作用促进了膜重塑的空间和时间协调。