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Ghost muscle fibres reconstituted with myosin heads labeled with the fluorescent probe 1,5-IAEDANS were used for analysis of muscle fibre dysfunction associated with the R133W mutation in β-tropomyosin (Tpm2.2). By using polarized microscopy, we showed that at high Ca2+ the R133W mutation in both αβ-Tpm heterodimers and ββ-Tpm homodimers decreases the amount of the myosin heads strongly bound to F-actin and the number of switched-on actin monomers, with this effect being stronger for ββ-Tpm. This mutation also inhibits the shifting of the R133W-Tpm strands towards the open position and the efficiency of the cross-bridge work. At low Ca2+, the amount of the strongly bound myosin heads is lower for R133W-Tpms than for WT-Tpms which may contribute to a low myofilament Ca2+-sensitivity of the R133W-Tpms. It is concluded that freezing of the mutant αβ- or ββ-Tpm close to the blocked position inhibits the strong binding of the cross-bridges and the switching on of actin monomers which may be the reason for muscle weakness associated with the R133W mutation in β-tropomyosin. The use of reagents that activate myosin may be appropriate to restore muscle function in patients with the R133W mutation.

Original publication




Journal article


Biochem Biophys Res Commun

Publication Date





258 - 262


Molecular mechanisms, Muscle contraction regulation, Muscle fibre, Nemaline myopathy, Tropomyosin mutation