Interactions Of Variable Domain (Vd) Of Drp1 With Lipids Revealed By Md Simulations

Fission proteins play a critical role in regulating the dynamics of cellular membranes. These proteins self-assemble on highly constricted membrane domains enabling membranes to undergo fission via the hemifission pathway. Here, we use the variable domain (VD) of Dynamin-related protein 1 (Drp1) as a model protein to investigate its interactions with a few key membrane remodeling lipids. The simulations reveal the preferential aggregation of these lipids with the lipid-binding motif in VD and lipid-dependent structural transformations. We further investigate these findings with selective mutations of VD to comprehend molecular underpinnings. Our results reveal a unique synergy between protein segments and lipids, where the two regulate each others' structural properties as well as membrane remodeling capabilities.