Myosin-binding protein C (MyBP-C) in cardiac muscle and contractility.
Both the MyBP-C motif between C1 and C2 and the C5 module are important regions for implementing the effect of MyBP-C on myosin and on contractility but in different ways. C5 may determine the folding of MyBP-C and the manner in which MyBP-C interacts with myosin. In spite of its apparent importance this interaction does not appear to be physiologically regulated. Its alteration by mutation however can have a major effect on contractility. On the other hand, the effect of the motif is regulated by phosphorylation and appears to be an important part of a physiological mechanism(s) for modulating contractility. Thick filaments isolated from cardiac muscle exist in one of three different structures (Levine et al 2001). Different degrees of phosphorylation of MyBP-C can produce transitions among the three structures. The combination of the binding results of Flashman et al (2002) with the data of McClellan et al (2001) suggests that the C5 interaction with C8 is critical in maintaining the normal structure of thick filaments and the normal function of the force generators in the filaments. The cardiac-specific sequence in C5 and its normal interaction with another part of the same or a different MyBP-C may be required for the correct 3 dimensional shape of the three MyBP-C molecules at each locus in the C zone and the normal structure of the thick filament. The normal interactions may be necessary to allow transitions in binding and filament structure that are associated with phosphorylation of the MyBP-C motif.
Winegrad
Saul
S
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19072, USA.
D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D017510:Protein Folding; D020033:Protein Isoforms; D051381:Rats; D013997:Time Factors; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D009218:Myosins; D020033:Protein Isoforms; D000099163:Myosin Binding Protein C