ArticleScientific reports2017
The mechano-sensing role of the unique SH3 insertion in plakin domains revealed by Molecular Dynamics simulations.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Actomyosin forces trigger a conformational change in desmoplakin within desmosomes.Nature communications · 2025Article
- High-pressure freezing of mechanically stretched cells.Journal of microscopy · 2025Article
- Intermediate filaments and their associated molecules.Journal of biomedical research · 2025Article
- Mechanics of cell sheets: plectin as an integrator of cytoskeletal networks.Open biology · 2025Review
- Desmosomes at a glance.Journal of cell science · 2024Review
- How cytoskeletal crosstalk makes cells move: Bridging cell-free and cell studies.Biophysics reviews · 2024Review
- Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions.European journal of human genetics : EJHG · 2024Article
- Biomaterial-based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration.Military Medical Research · 2024Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
- Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back.Frontiers in cell and developmental biology · 2022Review
- Review
- Review
- Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design.Journal of cardiovascular development and disease · 2020Review
- Scaling up single-cell mechanics to multicellular tissues - the role of the intermediate filament-desmosome network.Journal of cell science · 2020Review
- Mechanical Unfolding of Spectrin Repeats Induces Water-Molecule Ordering.Biophysical journal · 2020Article
- Dsg2 Upregulation as a Rescue Mechanism in Pemphigus.Frontiers in immunology · 2020Article
- The plakin domain ofDevelopment (Cambridge, England) · 2019Article
- Biomedical potential of mammalian spectraplakin proteins: Progress and prospect.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- [Research advances in limb-girdle muscular dystrophy type 2Q].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Review
- Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradation.JCI insight · 2019Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The plakin family of proteins, important actors in cross-linking force-bearing structures in the cell, contain a curious SH3 domain insertion in their chain of spectrin repeats (SRs). While SH3 domains are known to mediate protein-protein interactions, here, its canonical binding site is autoinhibited by the preceding SR. Under force, however, this SH3 domain could be released, and possibly launch a signaling cascade. We performed large-scale force-probe molecular dynamics simulations, across two orders of magnitude of loading rates, to test this hypothesis, on two prominent members of the plakin family: desmoplakin and plectin, obligate proteins at desmosomes and hemidesmosomes, respectively. Our simulations show that force unravels the SRs and abolishes the autoinhibition of the SH3 domain, an event well separated from the unfolding of this domain. The SH3 domain is free and fully functional for a significant portion of the unfolding trajectories. The rupture forces required for the two proteins significantly decrease when the SH3 domain is removed, which implies that the SH3 domain also stabilizes this junction. Our results persist across all simulations, and support a force-sensing as well as a stabilizing role of the unique SH3 insertion, putting forward this protein family as a new class of mechano-sensors.
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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.