Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.

Abstract	The Wiskott-Aldrich-syndrome protein (WASP) regulates polymerization of actin by the Arp2/3 complex. Here we show, using fluorescence anisotropy assays, that the carboxy-terminal WA domain of WASP binds to a single actin monomer with a Kd of 0.6 microM in an equilibrium with rapid exchange rates. Both WH-2 and CA sequences contribute to actin binding. A favourable DeltaH of -10 kcal mol(-1) drives binding. The WA domain binds to the Arp2/3 complex with a Kd of 0.9 microM; both the C and A sequences contribute to binding to the Arp2/3 complex. Wiskott-Aldrich-syndrome mutations in the WA domain that alter nucleation by the Arp2/3 complex over a tenfold range without affecting affinity for actin or the Arp2/3 complex indicate that there may be an activation step in the nucleation pathway. Actin filaments stimulate nucleation by producing a fivefold increase in the affinity of WASP-WA for the Arp2/3 complex.
Authors	J B Marchand, D A Kaiser, T D Pollard, H N Higgs
Journal	Nature cell biology (Nat Cell Biol) Vol. 3 Issue 1 Pg. 76-82 (Jan 2001) ISSN: 1465-7392 [Print] England
PMID	11146629 (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 Cytoskeletal Proteins Proteins Rhodamines WAS protein, human WASF1 protein, human Wiskott-Aldrich Syndrome Protein Wiskott-Aldrich Syndrome Protein Family
Topics	Actin Cytoskeleton (metabolism) Actin-Related Protein 2 Actin-Related Protein 3 Actins (metabolism) Animals Binding Sites (physiology) Cell Movement (physiology) Cytoskeletal Proteins Cytoskeleton (metabolism, ultrastructure) Fluorescence Polarization (methods, statistics & numerical data) Humans Point Mutation (physiology) Protein Structure, Tertiary (physiology) Proteins (chemistry, genetics, metabolism) Rabbits Rhodamines Wiskott-Aldrich Syndrome Protein Wiskott-Aldrich Syndrome Protein Family

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