title: Structure, interactions and function of the N-terminus of cardiac myosin binding protein C (MyBP-C): who does what, with what, and to whom?
abstract: The thick filament protein myosin-binding protein-C shows a highly modular architecture, with the C-terminal region responsible for tethering to the myosin and titin backbone of the thick filament. The N-terminal region shows the most significant differences between cardiac and skeletal muscle isogenes: an entire Ig-domain (C0) is added, together with highly regulated phosphorylation sites between Ig domains C1 and C2. These structural and functional differences at the N-terminus reflect important functions in cardiac muscle regulation in health and disease. Alternative interactions of this part of MyBP-C with the head-tail (S1-S2) junction of myosin or to actin filaments have been proposed, but with conflicting experimental evidence. The regulation of myosin or actin interaction by phosphorylation of the cardiac MyBP-C N-terminus may play an additional role in length-dependent contraction regulation. We discuss here the evidence for these proposed interactions, considering the required properties of MyBP-C, the way in which they may be regulated in muscle contraction and the way they might be related to heart disease. We also attempt to shed some light on experimental pitfalls and future strategies.
authors.affiliation: Randall Division for Cell and Molecular Biophysics and Cardiovascular Division, King's College London BHF Centre of Research Excellence, London, UK. mark.pfuhl@kcl.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Pfuhl
authors.forename: Mathias
authors.initials: M
authors.lastname: Gautel
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry*; D000199:Actins / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D024722:Cardiac Myosins / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry*; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012518:Sarcomeres / Q000737:chemistry*; D013329:Structure-Activity Relationship; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D024722:Cardiac Myosins; D002352:Carrier Proteins; D000099163:Myosin Binding Protein C