Clathrin self-assembly is mediated by a tandemly repeated superhelix

Clathrin is a triskelion-shaped cytoplasmic protein that polymerizes into a polyhedral lattice on intracellular membranes to form protein-coated membr ane vesicles. Lattice formation induces the sorting of membrane proteins du ring endocytosis and organelle biogenesis by interacting with membrane-asso ciated adaptor molecules(1). The clathrin triskelion is a trimer of heavy-c hain subunits (1,675 residues), each binding a single light-chain subunit, in the hub domain (residues 1,074-1,675), Light chains negatively modulate polymerization so that intracellular clathrin assembly is adaptor-dependent (2). Here we report the atomic structure, to 2.6 Angstrom resolution, of hu b residues 1,210-1,516 involved in mediating spontaneous clathrin heavy-cha in polymerization and light-chain association(3,4), The hub fragment folds into an elongated coil of alpha-helices, and alignment analyses reveal a 14 5-residue motif that is repeated seven times along the filamentous leg and appears in other proteins involved in vacuolar protein sorting. The resulti ng model provides a three-dimensional framework for understanding clathrin heavy-chain self-assembly, light-chain binding and trimerization.