ArticleProceedings of the National Academy of Sciences of the United States of America2012
Crystal structure of the S100A4-nonmuscle myosin IIA tail fragment complex reveals an asymmetric target binding mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Combined inhibition of S100A4 and TIGIT suppresses late-stage breast cancer metastasis.Cancer letters · 2026Article
- Dysregulation of Non-Muscle Myosin IIA Assembly and Phosphorylation in S100A4 Null Mouse Lens.Journal of cellular physiology · 2026Article
- Molecular Regulation of Secondary Hair Follicle Stem Cell by S100a4 in Cashmere Goat.International journal of molecular sciences · 2026Article
- S100A4/FSP1: A Prognostic Marker and a Promising Target for Antitumor Therapy.International journal of molecular sciences · 2025Review
- Covalent Inhibitors of S100A4 Block the Formation of a Pro-Metastasis Non-Muscle Myosin 2A Complex.Journal of medicinal chemistry · 2024Article
- Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024Review
- Structure, regulation, and mechanisms of nonmuscle myosin-2.Cellular and molecular life sciences : CMLS · 2024Review
- Essential role of CD38 in platelet aggregation through the PKC-mediated internalization and activation.BioImpacts : BI · 2024Article
- Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling.Acta pharmaceutica Sinica. B · 2022Article
- The Annexin A2/S100A10 Complex: The Mutualistic Symbiosis of Two Distinct Proteins.Biomolecules · 2021Review
- Studying the Structures of Relaxed and Fuzzy Interactions: The Diverse World of S100 Complexes.Frontiers in molecular biosciences · 2021Review
- Tumor-Suppressor p53TADChembiochem : a European journal of chemical biology · 2020Article
- S100A4 is activated by RhoA and catalyses the polymerization of non-muscle myosin, adhesion complex assembly and contraction in airway smooth muscle.The Journal of physiology · 2020Article
- Proteomimetic surface fragments distinguish targets by function.Chemical science · 2020Article
- NMMHC IIA triggers neuronal autophagic cell death by promoting F-actin-dependent ATG9A trafficking in cerebral ischemia/reperfusion.Cell death & disease · 2020Article
- Matrigel patterning reflects multicellular contractility.PLoS computational biology · 2019Article
- MYH9 Aggregation Induced by Direct Interaction With PRRSV GP5 Ectodomain Facilitates Viral Internalization by Permissive Cells.Frontiers in microbiology · 2019Article
- S100 proteins as therapeutic targets.Biophysical reviews · 2018Review
- Multiple S100 protein isoforms and C-terminal phosphorylation contribute to the paralog-selective regulation of nonmuscle myosin 2 filaments.The Journal of biological chemistry · 2018Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S100A4 is a member of the S100 family of calcium-binding proteins that is directly involved in tumor metastasis. It binds to the nonmuscle myosin IIA (NMIIA) tail near the assembly competence domain (ACD) promoting filament disassembly, which could be associated with increasing metastatic potential of tumor cells. Here, we investigate the mechanism of S100A4-NMIIA interaction based on binding studies and the crystal structure of S100A4 in complex with a 45-residue-long myosin heavy chain fragment. Interestingly, we also find that S100A4 binds as strongly to a homologous heavy chain fragment of nonmuscle myosin IIC as to NMIIA. The structure of the S100A4-NMIIA complex reveals a unique mode of interaction in the S100 family: A single, predominantly α-helical myosin chain is wrapped around the Ca(2+)-bound S100A4 dimer occupying both hydrophobic binding pockets. Thermal denaturation experiments of coiled-coil forming NMIIA fragments indicate that the coiled-coil partially unwinds upon S100A4 binding. Based on these results, we propose a model for NMIIA filament disassembly: Part of the random coil tailpiece and the C-terminal residues of the coiled-coil are wrapped around an S100A4 dimer disrupting the ACD and resulting in filament dissociation. The description of the complex will facilitate the design of specific drugs that interfere with the S100A4-NMIIA interaction.
Indexed as
Identifiers
What OpenQuestion holds
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.