Myopathic mutations in the β-chain of tropomyosin differently affect the structural and functional properties of ββ- and αβ-dimers.

Tropomyosin (Tpm) is an actin-binding protein that plays a vital role in the regulation of muscle contraction. Fast skeletal muscles express 2 Tpm isoforms, α (Tpm 1.1) and β (Tpm 2.2), resulting in the existence of 2 forms of dimeric Tpm molecule: αα-homodimer and αβ-heterodimer. ββ-Homodimer is unstable and absent in the native state, despite which most of the studies of myopathy-relating Tpm mutations have been performed on the ββ-homodimer. Here, we applied different methods to investigate the effects of myopathic mutations R133W and N202K in the β-chain of Tpm on properties of αβ-heterodimers and to compare them with the features of ββ-homodimers with the same mutations. The results show that properties of αβ-Tpm and ββ-Tpm with substitutions in the β-chain differ significantly, and this indicates that the effects of myopathic mutations in the Tpm β-chain should be studied on the Tpm αβ-heterodimer.-Bershitsky, S. Y., Logvinova, D. S., Shchepkin, D. V., Kopylova, G. V., Matyushenko, A. M. Myopathic mutations in the β-chain of tropomyosin differently affect the structural and functional properties of ββ- and αβ-dimers.