ArticleBiophysical journal2013
Modeling the assembly of the multiple domains of α-actinin-4 and its role in actin cross-linking.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- In silico conformational dynamics of the α-actinin-2 actin-binding domain upon phosphorylation.Biophysical journal · 2026Article
- Force-modulated structural landscape of the catch bonding F-actin crosslinker α-actinin-4.bioRxiv : the preprint server for biology · 2026Article
- α-Actinin-4 recruits Shp2 into focal adhesions to potentiate ROCK2 activation in podocytes.Life science alliance · 2022Article
- The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia.International journal of molecular sciences · 2021Review
- Article
- Postmitotic expansion of cell nuclei requires nuclear actin filament bundling by α-actinin 4.EMBO reports · 2020Article
- Focal segmental glomerulosclerosis ACTN4 mutants binding to actin: regulation by phosphomimetic mutations.Scientific reports · 2019Article
- Proteins with calmodulin-like domains: structures and functional roles.Cellular and molecular life sciences : CMLS · 2019Review
- Tyro3-mediated phosphorylation of ACTN4 at tyrosines is FAK-dependent and decreases susceptibility to cleavage by m-Calpain.The international journal of biochemistry & cell biology · 2018Article
- Comparative iTRAQ proteomics revealed proteins associated with horn development in yak.Proteome science · 2018Article
- The fifth sense: Mechanosensory regulation of alpha-actinin-4 and its relevance for cancer metastasis.Seminars in cell & developmental biology · 2017Review
- Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1.Scientific reports · 2016Article
- Synaptopodin couples epithelial contractility to α-actinin-4-dependent junction maturation.The Journal of cell biology · 2015Article
- Tandem phosphorylation within an intrinsically disordered region regulates ACTN4 function.Science signaling · 2015Article
- α-Actinin-4 is required for amoeboid-type invasiveness of melanoma cells.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The assembly of proteins into multidomain complexes is critical for their function. In eukaryotic nonmuscle cells, regulation of the homodimeric actin cross-linking protein α-actinin-4 (ACTN4) during cell migration involves signaling receptors with intrinsic tyrosine kinase activity, yet the underlying molecular mechanisms are poorly understood. As a first step to address the latter, we validate here an atomic model for the ACTN4 end region, which corresponds to a ternary complex between the N-terminal actin-binding domain (ABD) and an adjacent helical neck region of one monomer, and the C-terminal calmodulin-like domain of the opposite antiparallel monomer. Mutagenesis experiments designed to disrupt this ternary complex confirm that its formation reduces binding to F-actin. Molecular dynamics simulations show that the phosphomimic mutation Y265E increases actin binding by breaking several interactions that tether the two calponin homology domains into a closed ABD conformation. Simulations also show a disorder-to-order transition in the double phosphomimic mutant Y4E/Y31E of the 45-residue ACTN4 N-terminal region, which can inhibit actin binding by latching both calponin homology domains more tightly. Collectively, these studies provide a starting point for understanding the role of external cues in regulating ACTN4, with different phenotypes resulting from changes in the multidomain assembly of the protein.
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