Pseudophosphorylation of cardiac myosin regulatory light chain: a promising new tool for treatment of cardiomyopathy

Biophysics Reviews
Sunil Yadav, Danuta Szczesna-Cordary

Abstract

Many genetic mutations in sarcomeric proteins, including the cardiac myosin regulatory light chain (RLC) encoded by the MYL2 gene, have been implicated in familial cardiomyopathies. Yet, the molecular mechanisms by which these mutant proteins regulate cardiac muscle mechanics in health and disease remain poorly understood. Evidence has been accumulating that RLC phosphorylation has an influential role in striated muscle contraction and, in addition to the conventional modulation via Ca(2+) binding to troponin C, it can regulate cardiac muscle function. In this review, we focus on RLC mutations that have been reported to cause cardiomyopathy phenotypes via compromised RLC phosphorylation and elaborate on pseudo-phosphorylation rescue mechanisms. This new methodology has been discussed as an emerging exploratory tool to understand the role of phosphorylation as well as a genetic modality to prevent/rescue cardiomyopathy phenotypes. Finally, we summarize structural effects post-phosphorylation, a phenomenon that leads to an ordered shift in the myosin S1 and RLC conformational equilibrium between two distinct states.

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Citations

May 19, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Sunil YadavDanuta Szczesna-Cordary
Aug 2, 2018·International Journal of Molecular Sciences·Petr G Vikhorev, Natalia N Vikhoreva
Mar 20, 2021·The Journal of General Physiology·Christopher Solís, R John Solaro
May 1, 2021·International Journal of Molecular Sciences·Kasturi MarkandranChristine Cheung
May 21, 2021·The Journal of General Physiology·Yoel H SitbonDanuta Szczesna-Cordary
Oct 8, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masaaki ItoKaoru Dohi

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Methods Mentioned

BETA
transgenic
exome sequencing
motility assays

Software Mentioned

PyMOL
Exome

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