title: Clathrin self-assembly is mediated by a tandemly repeated superhelix.
abstract: Clathrin is a triskelion-shaped cytoplasmic protein that polymerizes into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. The clathrin triskelion is a trimer of heavy-chain 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. Here we report the atomic structure, to 2.6 A resolution, of hub residues 1,210-1,516 involved in mediating spontaneous clathrin heavy-chain polymerization and light-chain association. The hub fragment folds into an elongated coil of alpha-helices, and alignment analyses reveal a 145-residue motif that is repeated seven times along the filamentous leg and appears in other proteins involved in vacuolar protein sorting. The resulting model provides a three-dimensional framework for understanding clathrin heavy-chain self-assembly, light-chain binding and trimerization.
authors.affiliation: The G. W. Hooper Foundation, Department of Microbiology and Immunology, University of California San Francisco, 94143, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Ybe
authors.forename: F M
authors.initials: FM
authors.lastname: Brodsky
authors.forename: K
authors.initials: K
authors.lastname: Hofmann
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.forename: S H
authors.initials: SH
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: T N
authors.initials: TN
authors.lastname: Earnest
authors.forename: R J
authors.initials: RJ
authors.lastname: Fletterick
authors.forename: P K
authors.initials: PK
authors.lastname: Hwang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002966:Clathrin / Q000737:chemistry*; D003461:Crystallography; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid
chemical_list: D002966:Clathrin