Activation of the Arp2/3 complex by the Listeria acta protein. Acta binds two actin monomers and three subunits of the Arp2/3 complex.

Abstract	ActA is a bacterially encoded protein that enables Listeria monocytogenes to hijack the host cell actin cytoskeleton. It promotes Arp2/3-dependent actin nucleation, but its interactions with cellular components of the nucleation machinery are not well understood. Here we show that two domains of ActA (residues 85-104 and 121-138) with sequence similarity to WASP homology 2 domains bind two actin monomers with submicromolar affinity. ActA binds Arp2/3 with a K(d) of 0.6 microm and competes for binding with the WASP family proteins N-WASP and Scar1. By chemical cross-linking, ActA, N-WASP, and Scar1 contact the same three subunits of the Arp2/3 complex, p40, Arp2, and Arp3. Interestingly, profilin competes with ActA for binding of Arp2/3, but actophorin (cofilin) does not. The minimal Arp2/3-binding site of ActA (residues 144-170) is C-terminal to both actin-binding sites and shares sequence homology with Arp2/3-binding regions of WASP family proteins. The maximal activity at saturating concentrations of ActA is identical to the most active domains of the WASP family proteins. We propose that ActA and endogenous WASP family proteins promote Arp2/3-dependent nucleation by similar mechanisms and require simultaneous binding of Arp2 and Arp3.
Authors	J Zalevsky, I Grigorova, R D Mullins
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 5 Pg. 3468-75 (Feb 02 2001) ISSN: 0021-9258 [Print] United States
PMID	11029465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	ACTR2 protein, human ACTR3 protein, human Actin-Related Protein 2 Actin-Related Protein 3 Actins Bacterial Proteins Cytoskeletal Proteins Membrane Proteins Microfilament Proteins Wiskott-Aldrich Syndrome Protein Family actA protein, Listeria monocytogenes
Topics	Actin-Related Protein 2 Actin-Related Protein 3 Actins (metabolism) Amino Acid Motifs Amino Acid Sequence Animals Bacterial Proteins (pharmacology) Binding Sites Cytoskeletal Proteins Humans Kinetics Listeria monocytogenes (chemistry) Membrane Proteins (pharmacology) Microfilament Proteins (metabolism) Molecular Sequence Data Rats Sequence Homology, Amino Acid Wiskott-Aldrich Syndrome Protein Family

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