Hierarchical Regulation of WASP/WAVE Proteins
Hierarchical Regulation of WASP/WAVE Proteins
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.
- University of Massachusetts Medical School United States
- Howard Hughes Medical Institute United States
- The University of Texas Southwestern Medical Center United States
570, Protein Folding, Binding Sites, Protein Conformation, Cell Membrane, 590, Cell Biology, Actins, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein Family, Kinetics, Allosteric Regulation, Image Processing, Computer-Assisted, Homeostasis, Humans, Molecular Biology, Dimerization, Wiskott-Aldrich Syndrome Protein
570, Protein Folding, Binding Sites, Protein Conformation, Cell Membrane, 590, Cell Biology, Actins, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein Family, Kinetics, Allosteric Regulation, Image Processing, Computer-Assisted, Homeostasis, Humans, Molecular Biology, Dimerization, Wiskott-Aldrich Syndrome Protein
9 Research products, page 1 of 1
- 2010IsAmongTopNSimilarDocuments
- 2015IsAmongTopNSimilarDocuments
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2010IsAmongTopNSimilarDocuments
- 2010IsAmongTopNSimilarDocuments
- 2003IsAmongTopNSimilarDocuments
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).183 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
