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The reason for a high Ca2+-sensitivity associated with Arg91Gly substitution in TPM2 gene is the abnormal behavior and high flexibility of tropomyosin during the ATPase cycle.
Borovikov YS, Simonyan AO, Karpicheva OE, Avrova SV, Rysev NA, Sirenko VV, Piers A, Redwood CS. Borovikov YS, et al. Among authors: rysev na. Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):681-686. doi: 10.1016/j.bbrc.2017.10.161. Epub 2017 Oct 31. Biochem Biophys Res Commun. 2017. PMID: 29097206
Deviations in conformational rearrangements of thin filaments and myosin caused by the Ala155Thr substitution in hydrophobic core of tropomyosin.
Karpicheva OE, Sirenko VV, Rysev NA, Simonyan AO, Borys D, Moraczewska J, Borovikov YS. Karpicheva OE, et al. Among authors: rysev na. Biochim Biophys Acta Proteins Proteom. 2017 Dec;1865(12):1790-1799. doi: 10.1016/j.bbapap.2017.09.008. Epub 2017 Sep 20. Biochim Biophys Acta Proteins Proteom. 2017. PMID: 28939420
The reason for the low Ca2+-sensitivity of thin filaments associated with the Glu41Lys mutation in the TPM2 gene is "freezing" of tropomyosin near the outer domain of actin and inhibition of actin monomer switching off during the ATPase cycle.
Avrova SV, Karpicheva OE, Rysev NA, Simonyan AO, Sirenko VV, Redwood CS, Borovikov YS. Avrova SV, et al. Among authors: rysev na. Biochem Biophys Res Commun. 2018 Jul 12;502(2):209-214. doi: 10.1016/j.bbrc.2018.05.145. Epub 2018 May 26. Biochem Biophys Res Commun. 2018. PMID: 29792862
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