title: Molecular mechanics of cardiac myosin-binding protein C in native thick filaments.
abstract: 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.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Previs
authors.forename: S
authors.initials: S
authors.lastname: Beck Previs
authors.forename: J
authors.initials: J
authors.lastname: Gulick
authors.forename: J
authors.initials: J
authors.lastname: Robbins
authors.forename: D M
authors.initials: DM
authors.lastname: Warshaw
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000205:Actomyosin / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009210:Myofibrils / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D059748:Proteolysis; D012518:Sarcomeres / Q000378:metabolism; D000099163:Myosin Binding Protein C
chemical_list: D000205:Actomyosin; D002352:Carrier Proteins; D009218:Myosins; D000099163:Myosin Binding Protein C