A conserved amphipathic helix in WASP/Scar proteins is essential for activation of Arp2/3 complex.

Abstract	Members of the Wiskott-Aldrich syndrome protein (WASP) family link Rho GTPase signaling pathways to the cytoskeleton through a multiprotein assembly called Arp2/3 complex. The C-terminal VCA regions (verprolin-homology, central hydrophobic, and acidic regions) of WASP and its relatives stimulate Arp2/3 complex to nucleate actin filament branches. Here we show by differential line broadening in NMR spectra that the C (central) and A (acidic) segments of VCA domains from WASP, N-WASP and Scar bind Arp2/3 complex. The C regions of these proteins have a conserved sequence motif consisting of hydrophobic residues and an arginine residue. Point mutations in this conserved sequence motif suggest that it forms an amphipathic helix that is required in biochemical assays for activation of Arp2/3 complex. Key residues in this motif are buried through contacts with the GTPase binding domain in the autoinhibited structure of WASP and N-WASP, indicating that sequestration of these residues is an important aspect of autoinhibition.
Authors	Sanjay C Panchal, Donald A Kaiser, Eduardo Torres, Thomas D Pollard, Michael K Rosen
Journal	Nature structural biology (Nat Struct Biol) Vol. 10 Issue 8 Pg. 591-8 (Aug 2003) ISSN: 1072-8368 [Print] United States
PMID	12872157 (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 Cytoskeletal Proteins Macromolecular Substances Multiprotein Complexes Proteins WAS protein, human Wiskott-Aldrich Syndrome Protein
Topics	Actin-Related Protein 2 Actin-Related Protein 3 Amino Acid Sequence Binding Sites Cytoskeletal Proteins (chemistry, metabolism) Humans Macromolecular Substances Models, Molecular Molecular Sequence Data Multiprotein Complexes Nuclear Magnetic Resonance, Biomolecular Protein Structure, Secondary Protein Structure, Tertiary Proteins (chemistry, genetics, metabolism) Sequence Homology, Amino Acid Signal Transduction Wiskott-Aldrich Syndrome Protein

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