The tilted helix model of dynamin oligomers

Abstract

Significance Hydrolysis of GTP leads to remodeling of dynamin helical collars and severing of the underlying membrane neck—a critical step in vesicle endocytosis. We use mathematical modeling to explore the mechanisms that regulate oligomer deformation. We find that orientation of dynamin’s pleckstrin homology domain relative to the membrane introduces tilt strain. Relaxation of this strain requires departure of the oligomer from its intrinsic helical shape. Nonuniform accumulation of strain along the length of the dynamin chain results in partial oligomer fragmentation. The results of our model are corroborated experimentally by atomic force microscopy measurements. Our analysis leads to a definition of the tilted helix: a surface curve that maintains a fixed angle between the curve normal and the surface normal. Dynamin proteins assemble into characteristic helical structures around necks of clathrin-coated membrane buds. Hydrolysis of dynamin-bound GTP results in both fission of the membrane neck and partial disruption of the dynamin oligomer. Imaging by atomic force microscopy reveals that, on GTP hydrolysis, dynamin oligomers undergo a dynamic remodeling and lose their distinctive helical shape. While breakup of the dynamin helix is a critical stage in clathrin-mediated endocytosis, the mechanism for this remodeling of the oligomer has not been resolved. In this paper, we formulate an analytical, elasticity-based model for the reshaping and disassembly of the dynamin scaffold. We predict that the shape of the oligomer is modulated by the orientation of dynamin’s pleckstrin homology (PH) domain relative to the underlying membrane. Our results indicate that tilt of the PH domain drives deformation and fragmentation of the oligomer, in agreement with experimental observations. This model motivated the introduction of the tilted helix: a curve that maintains a fixed angle between its normal and the normal of the embedding surface. Our findings highlight the importance of tilt as a key regulator of size and morphology of membrane-bound oligomers.