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Cardiac Myosin Binding Protein - Europe PMC

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Last Updated: 16 November 2022

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Cryo-electron microscopy reveals cardiac myosin binding protein-C M-domain interactions with the thin filament.

Cardiac myosin-binding protein C modulates cardiac contraction by direct interactions with cardiac thick and thin filaments. Although the positions of C0, C1 and C2 on cTF have been reported, the M-domain's binding site on the surface of the cTF is unknown. The M-domain communicates with actin via helix 3 of its ordered tri-helix bundle region, with actin as a result, according to this article, although the unstructured part of the M-domain does not have extensive interactions with actin. To develop a complete representation of the NTD binding to the cTF, we combined recently developed cTF's surface with the identities of all the four NTDs on its surface. The model predicts that the NTDs' interactions with the cTF will vary depending on the cTF's activation state.

Source link: https://europepmc.org/article/MED/36370805


Myosin-Binding Protein C Stabilizes, But Is Not the Sole Determinant of SRX Myosin in Cardiac Muscle

The myosin Super Relaxed state is critical to striated muscle growth and functional regulation. We investigated how MyBP-C and its particular domains contribute to establishing the SRX state of cardiac muscle, using transgenic MyBP-C null mice and those expressing MyBP-C with a 271 residue N-terminal truncation. The percentage of SRX myosin was highest in the C-zone and lowest in the D-zone, where it is further from the sarcomere center and lacks MyBP-C, indicating a possible role for MyBP-C in stabilizing the SRX state within the C-zone. Even in the absence of MyBP-C or its N-terminus, SRX myosin are enriching in the C-zone, an inherent bias must exist in the thick filament's construction to maintain the SRX state.

Source link: https://europepmc.org/article/PPR/PPR554292


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've used time-resolved fluorescence resonance energy transfer to identify cardiac myosin and F-actin's interactions, with cMyBP-C, focusing on the N-terminal zone. To determine interactions, We engineered intermolecular pairs of labeling locations between donor-labeled myosin regulatory light chain or F-actin and cMyBP-C. Phosphorylation shortened the interaction of cMyBP-C with both myosin and actin. These results elucidate binding of cMyBP-C to myosin or actin under physiological and pathological conditions, providing new molecular insight into the modulatory role of these protein-protein interactions in cardiac muscle contractility. The TR-FRET assays, according to further research, are useful for rapid and precise determination of quantitative binding for screening physiological parameters and compounds that influence cMyBP-C interactions with myosin or F-actin for therapeutic discovery. Hypertrophic cardiomyopathy is a hereditary heart disease that causes mutations in genes that encode cardiac muscle proteins, according to the author's statement. HCM mutations discovered in cardiac myosin binding protein-C binds to both myosin and actin to finely tune contractility. 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 unique variations in HCM mutant cMyBP-C binding to myosin versus actin. Our findings are valuable in terms of the development 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