GSBS Student Publications

Title

Hierarchical regulation of WASP/WAVE proteins

UMMS Affiliation

Department of Molecular Genetics and Microbiology

Date

11-11-2008

Document Type

Article

Medical Subject Headings

Actins; Allosteric Regulation; Binding Sites; Cell Membrane; Dimerization; Homeostasis; Humans; Image Processing, Computer-Assisted; Kinetics; Protein Conformation; Protein Folding; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein; Wiskott-Aldrich Syndrome Protein Family

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses.

Rights and Permissions

Citation: Mol Cell. 2008 Nov 7;32(3):426-38. Link to article on publisher's site

DOI of Published Version

10.1016/j.molcel.2008.10.012

Related Resources

Link to Article in PubMed

Journal Title

Molecular cell

PubMed ID

18995840