ArticleProceedings of the National Academy of Sciences of the United States of America2016
Role and structural mechanism of WASP-triggered conformational changes in branched actin filament nucleation by Arp2/3 complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Distinct Arp2/3 isocomplexes drive axonal actin ring assembly and integrity.Science advances · 2026Article
- Direct Actin Monomer Delivery is a WASP-specific Requirement for Arp2/3 Complex Activation.Journal of molecular biology · 2026Article
- Role of eCIRP in Mediating Post-ischemia Microglial Phagocytosis via TREM-2 Receptor: Insights from Porcine and Mouse Cellular Models.Molecular neurobiology · 2026Article
- Mechanism of Arp2/3 complex branch disassembly by human Coro7.Nature communications · 2025Article
- Arp2/3-mediated bidirectional actin assembly by SPIN90 dimers.Nature structural & molecular biology · 2025Article
- Activation of Arp2/3 complex by a SPIN90 dimer in linear actin-filament nucleation.Nature structural & molecular biology · 2025Article
- Genome-Wide Characterization and Analysis of theGenes · 2025Article
- Molecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NPF binding to Arp2 is allosterically linked to the release of ArpC5's N-terminal tail and conformational changes in Arp2/3 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.Journal of proteome research · 2024Article
- Regeneration of actin filament branches from the same Arp2/3 complex.Science advances · 2024Article
- Evolutionary diversification reveals distinct somatic versus germline cytoskeletal functions of the Arp2 branched actin nucleator protein.Current biology : CB · 2023Article
- Mechanism of synergistic activation of Arp2/3 complex by cortactin and WASP-family proteins.Nature communications · 2023Article
- Transition State of Arp2/3 Complex Activation by Actin-Bound Dimeric Nucleation-Promoting Factor.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Impact of Arp2/3 Complex Inhibition on Cytoskeleton Dynamics and Mitochondrial Function during Goat Oocyte Meiosis.Animals : an open access journal from MDPI · 2023Article
- Mechanism of actin filament branch formation by Arp2/3 complex revealed by a high-resolution cryo-EM structureof the branch junction.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Wound Healing from an Actin Cytoskeletal Perspective.Cold Spring Harbor perspectives in biology · 2022Review
- Structure of Arp2/3 complex at a branched actin filament junction resolved by single-particle cryo-electron microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Unconcerted conformational changes in Arp2/3 complex integrate multiple activating signals to assemble functional actin networks.Current biology : CB · 2022Article
- Dysregulated inflammasome activity in intestinal inflammation - Insights from patients with very early onset IBD.Frontiers in immunology · 2022Review
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4 authors.
Funding
Abstract
The Arp2/3 (Actin-related proteins 2/3) complex is activated by WASP (Wiskott-Aldrich syndrome protein) family proteins to nucleate branched actin filaments that are important for cellular motility. WASP recruits actin monomers to the complex and stimulates movement of Arp2 and Arp3 into a "short-pitch" conformation that mimics the arrangement of actin subunits within filaments. The relative contribution of these functions in Arp2/3 complex activation and the mechanism by which WASP stimulates the conformational change have been unknown. We purified budding yeast Arp2/3 complex held in or near the short-pitch conformation by an engineered covalent cross-link to determine if the WASP-induced conformational change is sufficient for activity. Remarkably, cross-linked Arp2/3 complex bypasses the need for WASP in activation and is more active than WASP-activated Arp2/3 complex. These data indicate that stimulation of the short-pitch conformation is the critical activating function of WASP and that monomer delivery is not a fundamental requirement for nucleation but is a specific requirement for WASP-mediated activation. During activation, WASP limits nucleation rates by releasing slowly from nascent branches. The cross-linked complex is inhibited by WASP's CA region, even though CA potently stimulates cross-linking, suggesting that slow WASP detachment masks the activating potential of the short-pitch conformational switch. We use structure-based mutations and WASP-Arp fusion chimeras to determine how WASP stimulates movement toward the short-pitch conformation. Our data indicate that WASP displaces the autoinhibitory Arp3 C-terminal tail from a hydrophobic groove at Arp3's barbed end to destabilize the inactive state, providing a mechanism by which WASP stimulates the short-pitch conformation and activates Arp2/3 complex.
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