N-Terminal Actin-Binding Site of Lmod2 Promotes Controlled Pointed End Elongation
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Le résumé fourni par la source
BACKGROUND: Lmods (leiomodins) are critical for the assembly and maintenance of thin filaments in striated muscles by allowing thin filament elongation at the pointed ends. Lmod2's elongation function has been linked to both actin-binding sites (ABSs) 2 and 3, while the existence and function of an N-terminal ABS1 has been debated. METHODS: To elucidate the little-known role of Lmod2's ABS1, we created a mutant (F64D/L69D/W72D/W73D: Lmod2-quadruple mutant) predicted to decrease the binding of ABS1 to actin. We analyzed the effect of the mutations using several in vitro, cellular, and in vivo assays. RESULTS: By disrupting the interaction of Lmod2 ABS1 with actin in isolated cardiomyocytes and in mice, we engineered a super Lmod2 that results in remarkably longer thin filaments. Structural analysis determined that ABS1 of Lmod2 binds to actin through a disordered region and an amphipathic α-helix. Analysis of the mutated ABS1 revealed that the helix is destroyed, and binding to actin is maintained only in the N-terminal disordered region of Lmod2 ABS1. CONCLUSIONS: These discoveries support a model of controlled thin filament pointed end elongation by Lmod2 and provide the first direct evidence of, as well as the structural and functional mechanistic basis for, Lmod2's physiological leaky cap activity.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- N-Terminal Actin-Binding Site of Lmod2 Promotes Controlled Pointed End Elongation
- Date Crossref
- 27/02/2026
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Arizona Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program pays non établi dans la noticeUniversité ou école supérieure
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Icahn School of Medicine at Mount Sinai Department of Medicine and Cardiovascular Research Institute pays non établi dans la noticeUniversité ou école supérieure
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Washington State University pays non établi dans la noticeUniversité ou école supérieure
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Voiland School of Chemical Engineering and Bioengineering pays non établi dans la noticeUniversité ou école supérieure
Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program — University of Arizona, Department of Medicine and Cardiovascular Research Institute — Icahn School of Medicine at Mount Sinai et Washington State University, avec 1 autre affiliation.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.