Tropomyosin (Tpm) is an alpha-helical coiled-coil actin-binding protein that plays a key role in the Ca2+-regulated contraction of striated muscles. Two Tpm isoforms, alpha (Tpm 1.1) and beta (Tpm 2.2), are expressed in fast skeletal muscles. These Tpm isoforms can form either alpha alpha and beta beta homodimers, or alpha beta heterodimers. However, only alpha alpha-Tpm and alpha beta-Tpm dimers are usually present in most of fast skeletal muscles, because beta beta-homodimers are relatively unstable and cannot exist under physiologic conditions. Nevertheless, the most of previous studies of myopathy-causing mutations in the Tpm beta-chains were performed on the beta beta-homodimers. In the present work, we applied different methods to investigate the effects of two myopathic mutations in the beta-chain, Q147P and K49del (i.e. deletion of Lys49), on structural and functional properties of Tpm alpha beta-heterodimers and to compare them with the properties of beta beta-homodimers carrying these mutations in both beta-chains. The results show that the properties of alpha beta-Tpm heterodimers with these mutations in the beta-chain differ significantly from the properties of beta beta-homodimers with the same substitutions in both beta-chains. This indicates that the alpha beta-heterodimer is a more appropriate model for studying the effects of myopathic mutations in the beta-chain of Tpm than the beta beta-homodimer which virtually does not exist in human skeletal muscles. (C) 2018 Elsevier Inc. All rights reserved.