Advanced searches left 3/3

Cardiac Myosin - Europe PMC

Summarized by Plex Scholar
Last Updated: 16 September 2022

* If you want to update the article please login/register

N-terminal cardiac myosin-binding protein C interactions with myosin and actin filaments using time-resolved FRET

Myosin binding protein-C is a sarcomeric protein that is responsible for normal contraction and relaxation of the heart. With cMyBP-C, we have used time-resolved fluorescence resonance energy transfer to determine cardiac myosin and F-actin's interactions, focusing on the N-terminal area. To find interactions, we engineered intermolecular pairs of labeling links between donor-labeled myosin regulatory light chain or F-actin and cMyBP-C. Phosphorylation reduced the interaction of cMyBP-C with both myosin and actin. These results elucidate bindin of cMyBP-C to myosin or actin under physiological and pathological conditions, providing new molecular insight into these protein-protein interactions in cardiac muscle contractility. These results also show that the TR-FRET assays are appropriate for rapid and accurate determination of quantitative binding for screening physiological conditions and compounds that influence cMyBP-C interactions with myosin or F-actin for therapeutic discovery. Hypertrophic cardiomyopathy is a hereditary heart disease characterized by mutations in gene encoding cardiac muscle proteins. Significance Statement Hypertrophic cardiomyopathy is a hereditary heart disease linked to genetic mutations. To finely tune contractility, mutations found in cardiac myosin binding protein-C are a common cause of inherited HCM mutations. In a high-throughput plate reader form, we have created a series of Time-Resolved Fluorescence Resonance Energy Transfer assays that show the phosphorylation-sensitive binding of N-terminal cMyBP-C to myosin or actin. We observe altered binding due to phosphorylation and particular changes in HCM mutant cMyBP-C binding to myosin versus actin. Our results are instructive for the design of precision medicine screening assays and new therapies for HCM.

Source link: https://europepmc.org/article/PPR/PPR541839

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions