title: Alteration of myosin cross bridges by phosphorylation of myosin-binding protein C in cardiac muscle.
abstract: In addition to the contractile proteins actin and myosin, contractile filaments of striated muscle contain other proteins that are important for regulating the structure and the interaction of the two force-generating proteins. In the thin filaments, troponin and tropomyosin form a Ca-sensitive trigger that activates normal contraction when intracellular Ca is elevated. In the thick filament, there are several myosin-binding proteins whose functions are unclear. Among these is the myosin-binding protein C (MBP-C). The cardiac isoform contains four phosphorylation sites under the control of cAMP and calmodulin-regulated kinases, whereas the skeletal isoform contains only one such site, suggesting that phosphorylation in cardiac muscle has a specific regulatory function. We isolated natural thick filaments from cardiac muscle and, using electron microscopy and optical diffraction, determined the effect of phosphorylation of MBP-C on cross bridges. The thickness of the filaments that had been treated with protein kinase A was increased where cross bridges were present. No change occurred in the central bare zone that is devoid of cross bridges. The intensity of the reflections along the 43-nm layer line, which is primarily due to the helical array of cross bridges, was increased, and the distance of the first peak reflection from the meridian along the 43-nm layer line was decreased. The results indicate that phosphorylation of MBP-C (i) extends the cross bridges from the backbone of the filament and (ii) increases their degree of order and/or alters their orientation. These changes could alter rate constants for attachment to and detachment from the thin filament and thereby modify force production in activated cardiac muscle.
authors.affiliation: Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia 19104-6085, USA.
authors.forename: A
authors.initials: A
authors.lastname: Weisberg
authors.forename: S
authors.initials: S
authors.lastname: Winegrad
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003461:Crystallography; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009206:Myocardium / Q000648:ultrastructure*; D009210:Myofibrils / Q000648:ultrastructure*; D009218:Myosins / Q000648:ultrastructure*; D016624:Negative Staining; D010507:Periodicity; D010766:Phosphorylation; D051381:Rats; D013347:Subcellular Fractions / Q000648:ultrastructure; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009218:Myosins; D000099163:Myosin Binding Protein C