(1) Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461
(2) Department of Molecular and Cell Biology, University of California, Berkeley, California 94720
(3) Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02142
Cytoskeletal rearrangement occurs in a wide range of biological processes including cell motility, maintenance of cell morphology, bacterial infection, cell differentiation and development and tumorigenesis. Regulation of the actin cytoskeleton by the actin crosslinking protein fimbrin (plastin) mediates all of these events. Fimbrin is a representative member of the largest class of actin crosslinking proteins. All members of this family contain two F-actin binding domains, necessary for crosslinking individual actin filaments into higher order networks. We have obtained crystals of one of the actin binding domains from fimbrin, that diffract to at least 3.0 Angstroms resolution. Ongoing crystallographic studies, using multiple isomorphous replacement, are being pursued. In combination with information from genetic and biochemical studies, this crystal structure will elucidate, for the entire family of proteins, the mechanisms involved in actin bundling which govern actin cytoskeletal rearrangement.