Amphipathic Motifs Regulate N-BAR Protein Endophilin B1 Auto-Inhibition and Drive Membrane Remodeling

Abstract

Membrane remodeling is a common theme in a wide 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, autophagy and apoptosis. We find that endophilin B1 assembles into helical scaffolds on model 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 binding and remodeling activity. Taken together, this study provides novel insight into a poorly understood member of the N-BAR protein family 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.