1DFC

CRYSTAL STRUCTURE OF HUMAN FASCIN, AN ACTIN-CROSSLINKING PROTEIN

Summary for 1DFC

• Entry DOI: 10.2210/pdb1dfc/pdb
• Descriptor: FASCIN (1 entity in total)
• Functional Keywords: beta-trefoil fold for all four domains, structural genomics, psi, protein structure initiative, new york sgx research center for structural genomics, nysgxrc, structural protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 109203.76

Authors

Fedorov, A.A.,Fedorov, E.V.,Ono, S.,Matsumura, F.,Almo, S.C.,Burley, S.K.,New York SGX Research Center for Structural Genomics (NYSGXRC) (deposition date: 1999-11-18, release date: 2000-11-22, Last modification date: 2024-02-07)

Primary citation

Sedeh, R.S.,Fedorov, A.A.,Fedorov, E.V.,Ono, S.,Matsumura, F.,Almo, S.C.,Bathe, M.
Structure, evolutionary conservation, and conformational dynamics of Homo sapiens fascin-1, an F-actin crosslinking protein.
J.Mol.Biol., 400:589-604, 2010

PubMed Abstract: Eukaryotes have several highly conserved actin-binding proteins that crosslink filamentous actin into compact ordered bundles present in distinct cytoskeletal processes, including microvilli, stereocilia and filopodia. Fascin is an actin-binding protein that is present predominantly in filopodia, which are believed to play a central role in normal and aberrant cell migration. An important outstanding question regards the molecular basis for the unique localization and functional properties of fascin compared with other actin crosslinking proteins. Here, we present the crystal structure of full-length Homo sapiens fascin-1, and examine its packing, conformational flexibility, and evolutionary sequence conservation. The structure reveals a novel arrangement of four tandem beta-trefoil domains that form a bi-lobed structure with approximate pseudo 2-fold symmetry. Each lobe has internal approximate pseudo 2-fold and pseudo 3-fold symmetry axes that are approximately perpendicular, with beta-hairpin triplets located symmetrically on opposite sides of each lobe that mutational data suggest are actin-binding domains. Sequence conservation analysis confirms the importance of hydrophobic core residues that stabilize the beta-trefoil fold, as well as interfacial residues that are likely to stabilize the overall fascin molecule. Sequence conservation also indicates highly conserved surface patches near the putative actin-binding domains of fascin, which conformational dynamics analysis suggests to be coupled via an allosteric mechanism that might have important functional implications for F-actin crosslinking by fascin.

PubMed: 20434460
DOI: 10.1016/j.jmb.2010.04.043

Experimental method

X-RAY DIFFRACTION (2.9 Å)