To date, there are a huge number of mutant variants described for the TPM1 gene, which encodes the cardiac isoform of tropomyosin (Tpm1.1). The effect of amino acid substitutions Ile92Met and Glu97Gln on the properties of Tpm1.1 was investigated. To establish the possible pathogenicity of these mutant variants, the authors obtained preparations of recombinant proteins of the cardiac isoform Tpm1.1 with amino acid substitutions and studied their effect on the structure of the tropomyosin molecule, on its interaction with F‑actin, and on the functional properties of mutant Tpms as part of a reconstructed thin filament in an in vitro motility assay. Using circular dichroism spectroscopy and differential scanning calorimetry, it was shown that both mutations reduce the stability of the tropomyosin molecule. These mutations led to changes in the parameters of the interaction of myosin with a thin filament in an in vitro motility assay. The most pronounced effect was observed for Tpm1.1 E97Q. The E97Q mutation led to a significant increase in the calcium sensitivity of the myosin-actin interaction of thin reconstructed filaments, which also show residual movement at low calcium concentrations in an in vitro motility assay. The replacement of I92M significantly reduced the rate of movement of thin filaments into the in vitro motility assay and the cooperative interaction of myosin with actin. The obtained data make it possible to confirm the pathogenic status of these mutations, which can be taken into account for correction of cardiac disorders among patients with these genetic changes.


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