Molecular Mechanics of Cardiac Myosin-Binding Protein C in Native Thick Filaments

See allHide authors and affiliations

Science  07 Sep 2012:
Vol. 337, Issue 6099, pp. 1215-1218
DOI: 10.1126/science.1223602

You are currently viewing the abstract.

View Full Text


The heart’s pumping capacity results from highly regulated interactions of actomyosin molecular motors. Mutations in the gene for a potential regulator of these motors, cardiac myosin-binding protein C (cMyBP-C), cause hypertrophic cardiomyopathy. However, cMyBP-C’s ability to modulate cardiac contractility is not well understood. Using single-particle fluorescence imaging techniques, transgenic protein expression, proteomics, and modeling, we found that cMyBP-C slowed actomyosin motion generation in native cardiac thick filaments. This mechanical effect was localized to where cMyBP-C resides within the thick filament (i.e., the C-zones) and was modulated by phosphorylation and site-specific proteolytic degradation. These results provide molecular insight into why cMyBP-C should be considered a member of a tripartite complex with actin and myosin that allows fine tuning of cardiac muscle contraction.

View Full Text