Clathrin Self-Assembly into Polyhedral Cages Studied by Computer Simulations

Abstract

Clathrin is a three-legged proteins that self-assembles into polyhedral cages with regulatory and mechanical functions in the formation of cargo-laden vesicles at the cell-membrane and trans Golgi network. The essential features of self-assembly are innate to clathrin, as cages are also formed in purified slightly acid solutions. Our simulations of this process using a highly coarse-grained clathrin model reveal that a non-uniform distribution of interactions over clathrin's surface, rather than its characteristic shape, holds the key to self-assembly [1]. The cages are polydisperse, with a strong preference for a small subset of all possible configurations with twelve pentagonal and a variable number of hexagonal faces. Based on the experimental critical assembly concentration, we deduce an average binding energy of ∼23kT per clathrin [2]. The simulations also answer the long-standing question of how a flat purely hexagonal clathrin lattice can produce a cage with twelve pentagons: the introduction of spontaneous curvature through a change of hub and/or knee puckers causes tensions that result in the release of dome-shaped fragments, which may subsequently grow into full cages by recruiting cytosolic clathrin [2].[1] Biophys. J. 99, 1231 (2010).[2] Traffic 12, 1407 (2011).View Large Image | View Hi-Res Image | Download PowerPoint Slide