Actin crosslinking proteins organize filamentous (F-) actin into higher order assemblies such as bundles and networks which are important for biological processes including cell motility, cytokinesis and tumorigenesis. Fimbrin is a representative member of the largest superfamily of actin crosslinkers which is characterized by a conserved 275 amino acid F-actin binding domain. We have determined the crystal structure of the N-terminal actin binding domain of human fimbrin (ABD1) to 2.4 E resolution, which represents the first high resolution structure of an actin-crosslinking domain. Initial characterization of ABD1 crystals was performed using synchrotron radiation at Brookhaven National Laboratory, Beamline X9B, where the crystals diffracted to at least 1.9 E resolution. ABD1 is an ellipsoid molecule of dimensions (60x40x40E 3, and has a novel fold Hcomposed of two calponin homology (CH) subdomains. CH domains may Hserve to target a number of proteins, including signaling proteins, to Hcytoskeletal components. In collaboration with David DeRosier, we Hhave now docked this x-ray structure into the 28E electron microscopic Hreconstruction of actin filaments decorated with a comparable Hfragmenet of fimbrin. This work has for the first time provided an Hatomic model for the crosslinked assembly.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001633-17
Application #
6205778
Study Section
Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
17
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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