title: Dimeric WH2 domains in Vibrio VopF promote actin filament barbed-end uncapping and assisted elongation.
abstract: Proteins containing repeats of the WASP homology 2 (WH2) actin-binding module are multifunctional regulators of actin nucleation and assembly. The bacterial effector VopF in Vibrio cholerae, like VopL in Vibrio parahaemolyticus, is a unique homodimer of three WH2 motifs linked by a C-terminal dimerization domain. We show that only the first and third WH2 domains of VopF bind G-actin in a non-nucleating, sequestered conformation. Moreover, dimeric WH2 domains in VopF give rise to unprecedented regulation of actin assembly. Specifically, two WH2 domains on opposite protomers of VopF direct filament assembly from actin or profilin-actin by binding terminal subunits and uncapping capping protein from barbed ends by a new mechanism. Thus, VopF does not nucleate filaments by capping a pointed-end F-actin hexamer. These properties may contribute to VopF pathogenicity, and they show how dimeric WH2 peptides may mediate processive filament growth.
authors.affiliation: Cytoskeleton Dynamics and Motility Group, Laboratoire d'Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pernier
authors.forename: Jozsef
authors.initials: J
authors.lastname: Orban
authors.forename: Balendu Sankara
authors.initials: BS
authors.lastname: Avvaru
authors.forename: Antoine
authors.initials: A
authors.lastname: Jégou
authors.forename: Guillaume
authors.initials: G
authors.lastname: Romet-Lemonne
authors.forename: Bérengère
authors.initials: B
authors.lastname: Guichard
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Carlier
mesh_terms: D051344:Actin Capping Proteins / Q000737:chemistry / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D051344:Actin Capping Proteins; D000199:Actins; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family
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