Abstract

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.

  Funding Agency

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

  Institution

Name
Albert Einstein College of Medicine
Department
Type
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Vongsvivut, Jitraporn; Fernandez, Jason; Ekgasit, Sanong et al. (2004) Characterization of supported cylinder-planar germanium waveguide sensors with synchrotron infrared radiation. Appl Spectrosc 58:143-51
Masip, Lluis; Pan, Jonathan L; Haldar, Suranjana et al. (2004) An engineered pathway for the formation of protein disulfide bonds. Science 303:1185-9
Huang, Raymond Y; Miller, Lisa M; Carlson, Cathy S et al. (2003) In situ chemistry of osteoporosis revealed by synchrotron infrared microspectroscopy. Bone 33:514-21
Rashidzadeh, Hassan; Khrapunov, Sergei; Chance, Mark R et al. (2003) Solution structure and interdomain interactions of the Saccharomyces cerevisiae ""TATA binding protein"" (TBP) probed by radiolytic protein footprinting. Biochemistry 42:3655-65
Uchida, Takeshi; Takamoto, Keiji; He, Qin et al. (2003) Multiple monovalent ion-dependent pathways for the folding of the L-21 Tetrahymena thermophila ribozyme. J Mol Biol 328:463-78
Taylor, Colleen M; Watton, Stephen P; Bryngelson, Peter A et al. (2003) Inner-sphere complexation of cobalt(II) 2,9-dimethyl-1,10-phenanthroline ([Co(neo)]2+) with commercial and sol-gel derived silica gel surfaces. Inorg Chem 42:312-20
Dewan, John C; Feeling-Taylor, Angela; Puius, Yoram A et al. (2002) Structure of mutant human carbonmonoxyhemoglobin C (betaE6K) at 2.0 A resolution. Acta Crystallogr D Biol Crystallogr 58:2038-42
Kiselar, J G; Maleknia, S D; Sullivan, M et al. (2002) Hydroxyl radical probe of protein surfaces using synchrotron X-ray radiolysis and mass spectrometry. Int J Radiat Biol 78:101-14
Swisher, Jennifer F; Su, Linhui J; Brenowitz, Michael et al. (2002) Productive folding to the native state by a group II intron ribozyme. J Mol Biol 315:297-310
Dhavan, Gauri M; Crothers, Donald M; Chance, Mark R et al. (2002) Concerted binding and bending of DNA by Escherichia coli integration host factor. J Mol Biol 315:1027-37

Showing the most recent 10 out of 68 publications