4GP0

The crystal structure of human fascin 1 R149A K150A R151A mutant

Summary for 4GP0

• Entry DOI: 10.2210/pdb4gp0/pdb
• Related: 4GOV 4GOY 4GP3
• Descriptor: Fascin, BROMIDE ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: beta-trefoil, actin bundling protein, cancer, metastasis, cell migration, actin-binding, phosphoprotein, protein binding, actin
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton: Q16658
• Total number of polymer chains: 2
• Total formula weight: 111952.56

Authors

Yang, S.Y.,Huang, F.K.,Huang, J.,Chen, S.,Jakoncic, J.,Leo-Macias, A.,Diaz-Avalos, R.,Chen, L.,Zhang, J.J.,Huang, X.Y. (deposition date: 2012-08-20, release date: 2012-11-28, Last modification date: 2023-09-13)

Primary citation

Yang, S.,Huang, F.K.,Huang, J.,Chen, S.,Jakoncic, J.,Leo-Macias, A.,Diaz-Avalos, R.,Chen, L.,Zhang, J.J.,Huang, X.Y.
Molecular mechanism of fascin function in filopodial formation.
J.Biol.Chem., 288:274-284, 2013

PubMed Abstract: Filopodia are cell surface protrusions that are essential for cell migration. This finger-like structure is supported by rigid tightly bundled actin filaments. The protein responsible for actin bundling in filopodia is fascin. However, the mechanism by which fascin functions in filopodial formation is not clear. Here we provide biochemical, cryo-electron tomographic, and x-ray crystal structural data demonstrating the unique structural characteristics of fascin. Systematic mutagenesis studies on 100 mutants of fascin indicate that there are two major actin-binding sites on fascin. Crystal structures of four fascin mutants reveal concerted conformational changes in fascin from inactive to active states in the process of actin bundling. Mutations in any one of the actin-binding sites impair the cellular function of fascin in filopodial formation. Altogether, our data reveal the molecular mechanism of fascin function in filopodial formation.

PubMed: 23184945
DOI: 10.1074/jbc.M112.427971

Experimental method

X-RAY DIFFRACTION (2.5 Å)