Effect of cardiac myosin-binding protein C on stability of the thick filament.
In contrast to skeletal muscle isoforms of myosin-binding protein C (MyBP-C), the cardiac isoform has 11 rather than 10 modules (labeled C0-C10, N-C terminus), three phosphorylation sites between C1 and C2, and 28 additional amino acids in C5. Within the C5-C10 region of cardiac MyBP-C (cMyBP-C) there are interactions between C5 and C8 as well as C7 and C10. Isolated skinned cardiac trabeculae were incubated with one of three recombinant fragments of cMyBP-C to interfere with interactions of endogenous C5. 2-10 microM C5 or C5-containing peptide fragments of cMyBP-C reversibly reduced Ca sensitivity without extracting myofibrillar protein. C2-C4 fragments had no effect. This result indicated that the region of cMyBP-C that contains C5 maintains a specific structural arrangement of myosin that helps set its contractile properties. Greater than 10 microM C5 caused skinned trabeculae to lose a substantial amount of cMyBP-C and some myosin heavy chain, resulting in irreversible decline in maximum Ca-activated force. MyBP-C appears to stabilize the structure of the thick filament and modulate the way in which myosin heads extend to the thin filament.
McClellan
G
G
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA.
Kulikovskaya
I
I
Flavigny
J
J
Carrier
L
L
Winegrad
S
S
D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009218:Myosins / Q000737:chemistry* / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D000099163:Myosin Binding Protein C
D002118:Calcium; D002352:Carrier Proteins; D009218:Myosins; D010446:Peptide Fragments; D000099163:Myosin Binding Protein C