Clathrin Self-Assembly into Polyhedral Cages by Computer Simulations

Abstract

Clathrins are three-legged proteins that self-assemble into polyhedral cages with important regulatory and mechanical functions in the formation of cargo-laden vesicles at the cell-membrane (endocytosis) and the trans Golgi complex. The essential features of self-assembly are innate to clathrins, as cages are also formed in purified slightly acid solutions. This bare-bones process has been simulated here for the first time, revealing that an asymmetric distribution of interactions along the leg's circumference, rather than clathrin's characteristic shape, holds the key to the self-assembly process. The global puckering of the triskelion determines the average cage size, while the distribution of pentagonal and hexagonal facets in the self-assembled cages follows a simple selection rule. Simulations of planar clathrin lattices indicate that the introduction of spontaneous curvature, through a change of the clathrins's puckers, does not make a plaque curl up into a cage, but instead the plaque releases dome-shaped fragments which may subsequently grow into cages by recruiting cytosolic clathrins.View Large Image | View Hi-Res Image | Download PowerPoint Slide