biostudies-literatureUnknown9Kazmierczak KIn this study, we investigated the rescue potential of two phosphomimetic mutants of the myosin regulatory light chain (RLC, <i>MYL2</i> gene), S15D, and T160D RLCs. S15D-RLC mimics phosphorylation of the established serine-15 site of the human cardiac RLC. T160D-RLC mimics the phosphorylation of threonine-160, identified by computational analysis as a high-score phosphorylation site of myosin RLC. Cardiac myosin and left ventricular papillary muscle (LVPM) fibers were isolated from a previously generated model of hypertrophic cardiomyopathy (HCM), Tg-R58Q, and Tg-wild-type (WT) mice. Muscle specimens were first depleted of endogenous RLC and then reconstituted with recombinant human cardiac S15D and T160D phosphomimetic RLCs. Preparations reconstituted with recombinant human cardiac WT-RLFrontiers in cardiovascular medicine988066https://www.ebi.ac.uk/biostudies/studies/S-EPMC9530205biostudies-literatureFunctional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.PMC9530205Kazmierczak KLiang JGomez-Guevara MSzczesna-Cordary DfalseFunctional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.In this study, we investigated the rescue potential of two phosphomimetic mutants of the myosin regulatory light chain (RLC, <i>MYL2</i> gene), S15D, and T160D RLCs. S15D-RLC mimics phosphorylation of the established serine-15 site of the human cardiac RLC. T160D-RLC mimics the phosphorylation of threonine-160, identified by computational analysis as a high-score phosphorylation site of myosin RLC. Cardiac myosin and left ventricular papillary muscle (LVPM) fibers were isolated from a previously generated model of hypertrophic cardiomyopathy (HCM), Tg-R58Q, and Tg-wild-type (WT) mice. Muscle specimens were first depleted of endogenous RLC and then reconstituted with recombinant human cardiac S15D and T160D phosphomimetic RLCs. Preparations reconstituted with recombinant human cardiac WT-RL2022-01-01T00:00:00Z20222025-04-05T07:08:33.029Z2024-11-12T02:43:24.512ZS-EPMC95302053620456510.3389/fcvm.2022.988066