Dimeric WH2 Domains in Vibrio VopF Promote Actin Filament Barbed-end Uncapping and Assisted Elongation

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2013 Aug 6

PMID 23912276

Citations 28

Authors

Julien Pernier

Jozsef Orban

Balendu Sankara Avvaru

Antoine Jegou

Guillaume Romet-Lemonne

Berengere Guichard

Marie-France Carlier

Affiliations

Soon will be listed here.

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.

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References

Oda T, Iwasa M, Aihara T, Maeda Y, Narita A . The nature of the globular- to fibrous-actin transition. Nature. 2009; 457(7228):441-5. DOI: 10.1038/nature07685. View

Fujiwara I, Remmert K, Hammer 3rd J . Direct observation of the uncapping of capping protein-capped actin filaments by CARMIL homology domain 3. J Biol Chem. 2009; 285(4):2707-20. PMC: 2807327. DOI: 10.1074/jbc.M109.031203. View

Carlier M, Husson C, Renault L, Didry D . Control of actin assembly by the WH2 domains and their multifunctional tandem repeats in Spire and Cordon-Bleu. Int Rev Cell Mol Biol. 2011; 290:55-85. DOI: 10.1016/B978-0-12-386037-8.00005-3. View

Ahuja R, Pinyol R, Reichenbach N, Custer L, Klingensmith J, Kessels M . Cordon-bleu is an actin nucleation factor and controls neuronal morphology. Cell. 2007; 131(2):337-50. PMC: 2507594. DOI: 10.1016/j.cell.2007.08.030. View

Paunola E, Mattila P, Lappalainen P . WH2 domain: a small, versatile adapter for actin monomers. FEBS Lett. 2002; 513(1):92-7. DOI: 10.1016/s0014-5793(01)03242-2. View

Rottner K, Stradal T . Actin dynamics and turnover in cell motility. Curr Opin Cell Biol. 2011; 23(5):569-78. DOI: 10.1016/j.ceb.2011.07.003. View

Jegou A, Niedermayer T, Orban J, Didry D, Lipowsky R, Carlier M . Individual actin filaments in a microfluidic flow reveal the mechanism of ATP hydrolysis and give insight into the properties of profilin. PLoS Biol. 2011; 9(9):e1001161. PMC: 3181223. DOI: 10.1371/journal.pbio.1001161. View

De La Cruz E, Ostap E, Brundage R, Reddy K, Sweeney H, Safer D . Thymosin-beta(4) changes the conformation and dynamics of actin monomers. Biophys J. 2000; 78(5):2516-27. PMC: 1300842. DOI: 10.1016/S0006-3495(00)76797-X. View

Insall R, Machesky L . Actin dynamics at the leading edge: from simple machinery to complex networks. Dev Cell. 2009; 17(3):310-22. DOI: 10.1016/j.devcel.2009.08.012. View

10.

Yamashita A, Maeda K, Maeda Y . Crystal structure of CapZ: structural basis for actin filament barbed end capping. EMBO J. 2003; 22(7):1529-38. PMC: 152911. DOI: 10.1093/emboj/cdg167. View

11.

Namgoong S, Boczkowska M, Glista M, Winkelman J, Rebowski G, Kovar D . Mechanism of actin filament nucleation by Vibrio VopL and implications for tandem W domain nucleation. Nat Struct Mol Biol. 2011; 18(9):1060-7. PMC: 3173040. DOI: 10.1038/nsmb.2109. View

12.

Quinlan M, Heuser J, Kerkhoff E, Mullins R . Drosophila Spire is an actin nucleation factor. Nature. 2005; 433(7024):382-8. DOI: 10.1038/nature03241. View

13.

Elzinga M, Phelan J . F-actin is intermolecularly crosslinked by N,N'-p-phenylenedimaleimide through lysine-191 and cysteine-374. Proc Natl Acad Sci U S A. 1984; 81(21):6599-602. PMC: 391977. DOI: 10.1073/pnas.81.21.6599. View

14.

Carroll E, Gerrelli D, Gasca S, Berg E, Beier D, Copp A . Cordon-bleu is a conserved gene involved in neural tube formation. Dev Biol. 2003; 262(1):16-31. DOI: 10.1016/s0012-1606(03)00323-3. View

15.

Haglund C, Choe J, Skau C, Kovar D, Welch M . Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility. Nat Cell Biol. 2010; 12(11):1057-63. PMC: 3136050. DOI: 10.1038/ncb2109. View

16.

Rottner K, Hanisch J, Campellone K . WASH, WHAMM and JMY: regulation of Arp2/3 complex and beyond. Trends Cell Biol. 2010; 20(11):650-61. DOI: 10.1016/j.tcb.2010.08.014. View

17.

Hernandez-Valladares M, Kim T, Kannan B, Tung A, Aguda A, Larsson M . Structural characterization of a capping protein interaction motif defines a family of actin filament regulators. Nat Struct Mol Biol. 2010; 17(4):497-503. PMC: 3150215. DOI: 10.1038/nsmb.1792. View

18.

Haglund C, Welch M . Pathogens and polymers: microbe-host interactions illuminate the cytoskeleton. J Cell Biol. 2011; 195(1):7-17. PMC: 3187711. DOI: 10.1083/jcb.201103148. View

19.

Van Troys M, Dewitte D, Goethals M, Carlier M, Vandekerckhove J, Ampe C . The actin binding site of thymosin beta 4 mapped by mutational analysis. EMBO J. 1996; 15(2):201-10. PMC: 449934. View

20.

Tripathi R, Kaithwas V, Dureja C, Raychaudhuri S . Alanine-scanning mutagenesis of WH2 domains of VopF reveals residues important for conferring lethality in a Saccharomyces cerevisiae model. Gene. 2013; 525(1):116-23. DOI: 10.1016/j.gene.2013.04.071. View