ArticleProceedings of the National Academy of Sciences of the United States of America2015
Allosteric N-WASP activation by an inter-SH3 domain linker in Nck.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Crosstalk Between Phase-Separated Membraneless Condensates and Membrane-Bound Organelles in Cellular Function and Disease.Advances in experimental medicine and biology · 2025Review
- Electrical Forces Improve Memory in Old Age.Reviews of physiology, biochemistry and pharmacology · 2025Review
- De novo designed YK peptides forming reversible amyloid for synthetic protein condensates in mammalian cells.Nature communications · 2024Article
- Predictive value analysis of the interaction network of Tks4 scaffold protein in colon cancer.Frontiers in molecular biosciences · 2024Article
- A single chlamydial protein reshapes the plasma membrane and serves as recruiting platform for central endocytic effector proteins.Communications biology · 2023Article
- NCK1 Modulates Neuronal Actin Dynamics and Promotes Dendritic Spine, Synapse, and Memory Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Principles Governing the Phase Separation of Multidomain Proteins.Biochemistry · 2022Review
- The relative binding position of Nck and Grb2 adaptors impacts actin-based motility of Vaccinia virus.eLife · 2022Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- Intracellular artificial supramolecules based on de novo designed Y15 peptides.Nature communications · 2021Article
- Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling.Human cell · 2020Article
- Article
- Computational analysis of the evolutionarily conserved Missing In Metastasis/Metastasis Suppressor 1 gene predicts novel interactions, regulatory regions and transcriptional control.Scientific reports · 2019Article
- LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation.The Journal of cell biology · 2019Article
- Revisiting Non-BRCA1/2 Familial Whole Exome Sequencing Datasets ImplicatesFrontiers in genetics · 2019Article
- Enteropathogenic E. coli relies on collaboration between the formin mDia1 and the Arp2/3 complex for actin pedestal biogenesis and maintenance.PLoS pathogens · 2018Article
- Expanding the Paradigm: Intrinsically Disordered Proteins and Allosteric Regulation.Journal of molecular biology · 2018Review
- Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.PLoS computational biology · 2018Article
- Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach.Frontiers in medicine · 2018Review
- Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Actin filament networks assemble on cellular membranes in response to signals that locally activate neural Wiskott-Aldrich-syndrome protein (N-WASP) and the Arp2/3 complex. An inactive conformation of N-WASP is stabilized by intramolecular contacts between the GTPase binding domain (GBD) and the C helix of the verprolin-homology, connector-helix, acidic motif (VCA) segment. Multiple SH3 domain-containing adapter proteins can bind and possibly activate N-WASP, but it remains unclear how such binding events relieve autoinhibition to unmask the VCA segment and activate the Arp2/3 complex. Here, we have used purified components to reconstitute a signaling cascade driven by membrane-localized Src homology 3 (SH3) adapters and N-WASP, resulting in the assembly of dynamic actin networks. Among six SH3 adapters tested, Nck was the most potent activator of N-WASP-driven actin assembly. We identify within Nck a previously unrecognized activation motif in a linker between the first two SH3 domains. This linker sequence, reminiscent of bacterial virulence factors, directly engages the N-WASP GBD and competes with VCA binding. Our results suggest that animals, like pathogenic bacteria, have evolved peptide motifs that allosterically activate N-WASP, leading to localized actin nucleation on cellular membranes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.