Key result
The G126R and G126R/D137L substitutions in the α-chain of tropomyosin led to a moderate increase in the bending stiffness of reconstructed thin filaments, whereas D137L did not.
Stabilizing mutations G126R and G126R/D137L in the α-chain of tropomyosin moderately increase the bending stiffness of reconstructed thin filaments containing αβ-heterodimers.
These stiffness changes merit mechanistic follow-up in disease models; extends biophysical data but leaves clinical relevance open.
We studied the effect of the replacement of two highly conserved noncanonical residues in the α-chain of tropomyosin, that is, Asp137 and Gly126, with the canonical residues, Leu and Arg, on the mechanical properties of reconstructed thin filaments that contain αβ-heterodimers of tropomyosin. For this purpose, the reconstructed thin filaments that contain fibrillar actin, tropomyosin, and troponin were stretched with an optical trap. The resulting strain–force diagrams were analyzed using a mathematical model proposed previously in order to estimate the bending stiffness. It was shown that the thin filaments that contain αβ-heterodimers of tropomyosin with α-chains of the pseudo-wild type, i.e., that contain the C190A substitution, have approximately the same bending stiffness as the filament with αα-homodimers of tropomyosin. The stabilizing substitution D137L in the α-chain of tropomyosin did not cause a statistically significant change in the bending stiffness of the filaments that contain αβ-heterodimers of tropomyosin, whereas the G126R and G126R/D137L substitutions led to a moderate increase in this stiffness. This increase in stiffness was, however, much less pronounced than that for the filaments that contain αα-homodimers of tropomyosin with these substitutions in both α-chains. The relationship between the results obtained in this study and the previously published data on the effects of these stabilizing substitutions in the α-chain of tropomyosin on the structural and functional properties of thin filaments with αβ-heterodimers of tropomyosin is discussed.
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Nabiev et al. (2018) studied this question. Stabilizing mutations (D137L, G126R, G126R/D137L) in the α-chain of tropomyosin vs. Pseudo-wild type (C190A) α-chain of tropomyosin was evaluated on Bending stiffness of reconstructed thin filaments. The G126R and G126R/D137L substitutions in the α-chain of tropomyosin led to a moderate increase in the bending stiffness of reconstructed thin filaments, whereas D137L did not.
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