ArticleBiophysical journal2018
Precise Binding of Tropomyosin on Actin Involves Sequence-Dependent Variance in Coiled-Coil Twisting.
Article in Biophysical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Evaluating Pathogenicity ofJournal of precision medicine (Amsterdam, Netherlands) · 2025Article
- Dual role of Tropomyosin-R160 in thin filament regulation: Insights into phosphorylation-dependent cardiac relaxation and cardiomyopathy mechanisms.Archives of biochemistry and biophysics · 2025Article
- Glutamate 139 of tropomyosin is critical for cardiac thin filament blocked-state stabilization.Journal of molecular and cellular cardiology · 2024Article
- Molecular Mechanisms of Deregulation of Muscle Contractility Caused by the R168H Mutation in TPM3 and Its Attenuation by Therapeutic Agents.International journal of molecular sciences · 2023Article
- Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.PNAS nexus · 2023Article
- Alternative splicing of a single exon causes a major impact on the affinity ofFrontiers in cell and developmental biology · 2023Article
- De Novo Asp219Val Mutation in Cardiac Tropomyosin Associated with Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Article
- Modeling Human Cardiac Thin Filament Structures.Frontiers in physiology · 2022Review
- Review
- Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7.International journal of molecular sciences · 2021Article
- Impact of A134 and E218 Amino Acid Residues of Tropomyosin on Its Flexibility and Function.International journal of molecular sciences · 2020Article
- Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by GlnInternational journal of molecular sciences · 2020Article
- Cryo-EM and Molecular Docking Shows Myosin Loop 4 Contacts Actin and Tropomyosin on Thin Filaments.Biophysical journal · 2020Article
- Protein-Protein Docking Reveals Dynamic Interactions of Tropomyosin on Actin Filaments.Biophysical journal · 2020Article
- Molecular Mechanisms of Muscle Weakness Associated with E173A Mutation in Tpm3.12. Troponin CaInternational journal of molecular sciences · 2020Article
- Functional outcomes of structural peculiarities of striated muscle tropomyosin.Journal of muscle research and cell motility · 2020Review
- A new twist on tropomyosin binding to actin filaments: perspectives on thin filament function, assembly and biomechanics.Journal of muscle research and cell motility · 2020Review
- Cardiomyopathy Mutation Alters End-to-End Junction of Tropomyosin and Reduces Calcium Sensitivity.Biophysical journal · 2020Article
- The Effect of Tropomyosin Mutations on Actin-Tropomyosin Binding: In Search of Lost Time.Biophysical journal · 2019Article
- The Primary Causes of Muscle Dysfunction Associated with the Point Mutations in Tpm3.12; Conformational Analysis of Mutant Proteins as a Tool for Classification of Myopathies.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Often considered an archetypal dimeric coiled coil, tropomyosin nonetheless exhibits distinctive "noncanonical" core residues located at the hydrophobic interface between its component α-helices. Notably, a charged aspartate, D137, takes the place of nonpolar residues otherwise present. Much speculation has been offered to rationalize potential local coiled-coil instability stemming from D137 and its effect on regulatory transitions of tropomyosin over actin filaments. Although experimental approaches such as electron cryomicroscopy reconstruction are optimal for defining average tropomyosin positions on actin filaments, to date, these methods have not captured the dynamics of tropomyosin residues clustered around position 137 or elsewhere. In contrast, computational biochemistry, involving molecular dynamics simulation, is a compelling choice to extend the understanding of local and global tropomyosin behavior on actin filaments at high resolution. Here, we report on molecular dynamics simulation of actin-free and actin-associated tropomyosin, showing noncanonical residue D137 as a locus for tropomyosin twist variation, with marked effects on actin-tropomyosin interactions. We conclude that D137-sponsored coiled-coil twisting is likely to optimize electrostatic side-chain contacts between tropomyosin and actin on the assembled thin filament, while offsetting disparities between tropomyosin pseudorepeat and actin subunit periodicities. We find that D137 has only minor local effects on tropomyosin coiled-coil flexibility, (i.e., on its flexural mobility). Indeed, D137-associated overtwisting may actually augment tropomyosin stiffness on actin filaments. Accordingly, such twisting-induced stiffness of tropomyosin is expected to enhance cooperative regulatory translocation of the tropomyosin cable over actin.
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