PDBsum entry 1dfc

Structural protein

PDB id: 1dfc

Contents

Protein chain

475 a.a. *

* Residue conservation analysis

PDB id:

1dfc

Name:

Structural protein

Title:

Crystal structure of human fascin, an actin-crosslinking protein

Structure:

Fascin. Chain: a, b. Fragment: full-length protein. Synonym: actin bundling protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.90Å R-factor: 0.184 R-free: 0.268

Authors:

A.A.Fedorov,E.V.Fedorov,S.Ono,F.Matsumura,S.C.Almo,S.K.Burley,New York Sgx Research Center For Structural Genomics (Nysgxrc)

Key ref:

R.S.Sedeh et al. (2010). Structure, evolutionary conservation, and conformational dynamics of Homo sapiens fascin-1, an F-actin crosslinking protein. J Mol Biol, 400, 589-604. PubMed id: 20434460

Date:

18-Nov-99 Release date: 22-Nov-00

Protein chains

Q16658  (FSCN1_HUMAN) -  Fascin from Homo sapiens

Seq: 493 a.a.

Struc: 475 a.a.

Enzyme reactions

• Enzyme class: E.C.?

J Mol Biol 400:589-604 (2010)

PubMed id: 20434460

Structure, evolutionary conservation, and conformational dynamics of Homo sapiens fascin-1, an F-actin crosslinking protein.

R.S.Sedeh, A.A.Fedorov, E.V.Fedorov, S.Ono, F.Matsumura, S.C.Almo, M.Bathe.

ABSTRACT

Eukaryotes employ several highly conserved actin-binding proteins to crosslink filamentous actin into compact ordered bundles present in distinct cytoskeletal processes including microvilli, stereocilia, and filopodia. Fascin is one such 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 structural 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, as well as 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-twofold symmetry. Each lobe has internal approximate pseudo-two-fold and pseudo-three-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 likely 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 suggest to be coupled via an allosteric mechanism that might have important functional implications for F-actin crosslinking by fascin.