Clathrin Structure Reveals Motifs for Self-Assembly
Clathrin is a protein that plays a major role in the creation of vesicles (membrane-bound transport packages) in cells. It forms a polyhedral (soccer-ball-shaped) lattice made up of many clathrin molecules that coats a new vesicle as it forms and also helps in protein sorting. To understand how clathrin works, particularly how it forms the lattice, scientists needed a clearer view of the protein's structure. At the Macromolecular Crystallography Facility at the ALS, a group of scientists from the University of California, San Francisco, and MEMOREC GmbH have solved the structure of a key part of this protein involved in the lattice assembly.
The clathrin molecule (above, left) is known to take the shape of a triskelion, a figure with three bent legs. The legs are joined at a central trimerization domain (txd). The leg structure was solved by multiple-wavelength anomalous diffraction (MAD) studies of a segment in the proximal domain. Formation of the polyhedral lattice (above, right) involves association of neighbor proximal domains (yellow) and neighbor distal domains (purple, beneath).
The researchers found the leg to be made up of a series of 10-helix repeats, seven such repeats making up one leg. Each repeat (clathrin heavy-chain repeat, or CHCR, above) shows two faces of helices (yellow and green cylinders) that probably associate with faces on neighbor triskelions in lattice self-assembly. In addition, the researchers found similar structures in other proteins involved in maintenance of vacuoles and protein sorting, suggesting a common coupling mechanism.
Research conducted by J.A. Ybe, F.M. Brodsky, K. Lin, S.-H. Liu, L. Chen, R.J. Fletterick, and P.K. Hwang (University of California, San Francisco); K. Hofmann (MEMOREC Stoffel GmbH); and T.N. Earnest (Berkeley Lab), using Beamline 5.0.2.
Funding: National Institutes of Health, U.S. Department of Energy.
Publication about this experiment: J.A. Ybe et al., Nature 399 (1999), 371-375.
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