ArticleStructure (London, England : 1993)2019
Non-syndromic Mitral Valve Dysplasia Mutation Changes the Force Resilience and Interaction of Human Filamin A.
Article in Structure (London, England : 1993), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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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.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- UltrastrongScience advances · 2025Article
- May the force be with you: The role of hyper-mechanostability of the bone sialoprotein binding protein during early stages ofFrontiers in chemistry · 2023Article
- Structure and Function of Filamin C in the Muscle Z-Disc.International journal of molecular sciences · 2020Review
- Streptavidin/biotin: Tethering geometry defines unbinding mechanics.Science advances · 2020Article
- Clinical exome sequencing revealed that FLNC variants contribute to the early diagnosis of cardiomyopathies in infant patients.Translational pediatrics · 2020Article
- Critical Structural Defects Explain Filamin A Mutations Causing Mitral Valve Dysplasia.Biophysical journal · 2019Article
- Mechanisms of Nanonewton Mechanostability in a Protein Complex Revealed by Molecular Dynamics Simulations and Single-Molecule Force Spectroscopy.Journal of the American Chemical Society · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Filamin A (FLNa), expressed in endocardial endothelia during fetal valve morphogenesis, is key in cardiac development. Missense mutations in FLNa cause non-syndromic mitral valve dysplasia (FLNA-MVD). Here, we aimed to reveal the currently unknown underlying molecular mechanism behind FLNA-MVD caused by the FLNa P637Q mutation. The solved crystal structure of the FLNa3-5 P637Q revealed that this mutation causes only minor structural changes close to mutation site. These changes were observed to significantly affect FLNa's ability to transmit cellular force and to interact with its binding partner. The performed steered molecular dynamics simulations showed that significantly lower forces are needed to split domains 4 and 5 in FLNA-MVD than with wild-type FLNa. The P637Q mutation was also observed to interfere with FLNa's interactions with the protein tyrosine phosphatase PTPN12. Our results provide a crucial step toward understanding the molecular bases behind FLNA-MVD, which is critical for the development of drug-based therapeutics.
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Registered trials
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