Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.
SG, R., SR, N., AM, K., GV, K., JY, A., SY, K., VV, M., DV, S., AM, M., & VV, N. (2026). Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.. Molecules (Basel, Switzerland). https://doi.org/10.3390/molecules31111784
SG R, SR N, AM K, GV K, JY A, SY K, et al. Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.. Molecules (Basel, Switzerland). 2026; doi: 10.3390/molecules31111784
SG R, SR N, AM K, et al. Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.[J]. Molecules (Basel, Switzerland). 2026. DOI: 10.3390/molecules31111784.
@article{sg2026,
author = {Roman SG and Nabiev SR and Kochurova AM and Kopylova GV and Antonets JY and Kleymenov SY and Mikhaylova VV and Shchepkin DV and Matyushenko AM and Nefedova VV},
title = {Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.},
journal = {Molecules (Basel, Switzerland)},
year = {2026},
doi = {10.3390/molecules31111784},
note = {PMID: 42280091},
}
TY - JOUR AU - Roman SG AU - Nabiev SR AU - Kochurova AM AU - Kopylova GV AU - Antonets JY AU - Kleymenov SY AU - Mikhaylova VV AU - Shchepkin DV AU - Matyushenko AM AU - Nefedova VV TI - Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7. T2 - Molecules (Basel, Switzerland) PY - 2026 DO - 10.3390/molecules31111784 AN - PMID:42280091 ER -
Tropomyosins (Tpm) are the family of actin-binding proteins encoded by four genes in humans. Missense mutations in the TPM1 gene associated with cardiomyopathies have been studied in the sarcomeric isoform Tpm1.1. The cardiomyopathy-causing mutations E40K and E54K are located in exon 2b of the TPM1 gene and may be expressed in non-muscle cytoplasmic Tpm isoforms, including Tpm1.7, which is associated with early tissue development. In the present work, we investigate the effects of mutations E40K and E54K on the properties of Tpm1.7. The E40K and E54K mutations caused destabilization of the Tpm1.7 molecule at the N- and C-termini parts. Neither mutation affected the Tpm1.7 affinity for filamentous actin (F-actin). The bending stiffness of F-actin/Tpm1.7 E40K filaments was lower compared to F-actin/Tpm1.7 WT (wild-type). The interplay of Tpm1.7 and motor proteins was studied in an in vitro motility assay with skeletal myosin. Tpm1.7 WT reduced the sliding velocity of F-actin by half; the velocity of F-actin with Tpm1.7 E54K did not differ from that of bare F-actin; and Tpm1.7 E40K decreased the F-actin velocity by approximately threefold. While Tpm1.7 E40K did not affect the protective effect of Tpm1.7 against F-actin severing by cofilin-1, the E54K mutation enhanced protection against cofilin-1. Thus, cardiomyopathic mutations in the TPM1 gene can affect the properties of non-muscle Tpm isoforms, which indicates that this should be taken into account when studying the molecular mechanisms of the pathogenesis of these diseases.