Isoform-specific interaction of the myosin-binding proteins (MyBPs) with skeletal and cardiac myosin is a property of the C-terminal immunoglobulin domain.
Full-length cDNAs encoding chicken and human skeletal MyBP-H and MyBP-C have been isolated and sequenced (1-5). All are members of a protein family with repetitive immunoglobulin C2 and fibronectin type III motifs. The myosin binding domain was mapped to a single immunoglobulin motif in cardiac MyBP-C and skeletal MyBP-H. Limited alpha-chymotryptic digestion of cardiac MyBP-C generated three peptides, similar in relative mobility to those of skeletal MyBP-C: approximately 100, 40, and 15 kDa. Tryptic digestion of MyBP-H yielded two peptides: approximately 50 and 14 kDa. Partial amino acid sequences proved that the 15- and 14-kDa fragments are located at the C termini of cardiac MyBP-C and skeletal MyBP-H, respectively. Only the 14- and 15-kDa peptides bound to myosin. Thus, the myosin binding site in all three proteins resides within an homologous, C-terminal immunoglobulin domain. Binding reactions (2) between the skeletal and cardiac MyBPs and corresponding myosin isoforms demonstrated saturable binding of the MyBP proteins and their C-terminal peptides to myosin, but there are higher limiting stoichiometries with the homologous isoform partners. Evidence is presented indicating that MyBP-H and -C compete for binding to a discrete number of sites in myosin filaments.
Alyonycheva
T N
TN
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021, USA.
Mikawa
T
T
Reinach
F C
FC
Fischman
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D007136:Immunoglobulins / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*
D002352:Carrier Proteins; D007136:Immunoglobulins; D010446:Peptide Fragments; D009218:Myosins