TY - JOUR
T1 - Cardiac myosin-binding protein C decorates F-actin
T2 - Implications for cardiac function
AU - Whitten, Andrew E.
AU - Jeffries, Cy M.
AU - Harris, Samantha P.
AU - Trewhella, Jill
PY - 2008/11/25
Y1 - 2008/11/25
N2 - Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin.
AB - Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin.
KW - C protein
KW - Familial hypertrophic cardiomypathy
KW - Muscle regulation
KW - Neutron contrast variation
KW - Small-angle scattering
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U2 - 10.1073/pnas.0808903105
DO - 10.1073/pnas.0808903105
M3 - Article
C2 - 19011110
AN - SCOPUS:57449111078
VL - 105
SP - 18360
EP - 18365
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 47
ER -