Letters to Nature
Nature 399, 371-375 (27 May 1999) | doi:10.1038/20708; Received 1 February 1999; Accepted 13 April 1999
Clathrin self-assembly is mediated by a tandemly repeated superhelix
Joel A. Ybe1, Frances M. Brodsky1, Kay Hofmann2, Kai Lin3,4, Shu-Hui Liu1, Lin Chen1, Thomas N. Earnest5, Robert J. Fletterick3 and Peter K. Hwang3
- The G. W. Hooper Foundation, Department of Microbiology and Immunology, Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry
- Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94143, USA
- Bioinformatics Group, MEMOREC Stoffel GmbH, Stoeckheimer Weg 1, 50829 Koeln, Germany
- Macromolecular Cyrstallography Facility at the Advanced Light Source, Physical Biosciences Division, Lawrence Berkeley National Laboraotry, Berkeley, California 94720, USA
- Present address: Department of Pharmacology, University of Massachusetts Medical Center, 55 Lake Ave. North Worcester, Massachusetts 01655, USA.
Correspondence to: Correspondence and requests for materials should be addressed to F.M.B. (e-mail: Email: fmarbro@itsa.ucsf.edu).The structural coordinates are available from the Brookhaven Protein Databank (ID code: 1b89).
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 molecules1. 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-dependent2. Here we report the atomic structure, to 2.6 Å resolution, of hub residues 1,210–1,516 involved in mediating spontaneous clathrin heavy-chain polymerization and light-chain association3,4. The hub fragment folds into an elongated coil of 
-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.