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Clathrin self-assembly is mediated by a tandemly repeated superhelix

Author

Listed:
  • Joel A. Ybe

    (G. W. Hooper Foundation)

  • Frances M. Brodsky

    (G. W. Hooper Foundation)

  • Kay Hofmann

    (Bioinformatics Group, MEMOREC Stoffel GmbH)

  • Kai Lin

    (University of California San Francisco
    University of Massachusetts Medical Center)

  • Shu-Hui Liu

    (G. W. Hooper Foundation)

  • Lin Chen

    (G. W. Hooper Foundation)

  • Thomas N. Earnest

    (Macromolecular Cyrstallography Facility at the Advanced Light Source, Lawrence Berkeley National Laboraotry)

  • Robert J. Fletterick

    (University of California San Francisco)

  • Peter K. Hwang

    (University of California San Francisco)

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 α-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.

Suggested Citation

  • Joel A. Ybe & Frances M. Brodsky & Kay Hofmann & Kai Lin & Shu-Hui Liu & Lin Chen & Thomas N. Earnest & Robert J. Fletterick & Peter K. Hwang, 1999. "Clathrin self-assembly is mediated by a tandemly repeated superhelix," Nature, Nature, vol. 399(6734), pages 371-375, May.
  • Handle: RePEc:nat:nature:v:399:y:1999:i:6734:d:10.1038_20708
    DOI: 10.1038/20708
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