Title

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

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

5-2003

Document Type

Article

Medical Subject Headings

Actin-Related Protein 2; Actin-Related Protein 3; Amino Acid Sequence; Binding Sites; Cytoskeletal Proteins; Humans; Macromolecular Substances; Models, Molecular; Molecular Sequence Data; Multiprotein Complexes; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Sequence Homology, Amino Acid; Signal Transduction; Wiskott-Aldrich Syndrome Protein

Disciplines

Genetics and Genomics | Molecular Biology | Structural Biology

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.

Rights and Permissions

Citation: Nat Struct Biol. 2003 Aug;10(8):591-8. Link to article on publisher's site

Comments

At the time of publication, Eduardo Torres was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

12872157