Calcium-Dependent Interaction Occurs between Slow Skeletal Myosin Binding Protein C and Calmodulin
AbstractMyosin binding protein C (MyBP-C) is a multi-domain protein that participates in the regulation of muscle contraction through dynamic interactions with actin and myosin. Three primary isoforms of MyBP-C exist: cardiac (cMyBP-C), fast skeletal (fsMyBP-C), and slow skeletal (ssMyBP-C). The N-terminal region of cMyBP-C contains the M-motif, a three-helix bundle that binds Ca2+-loaded calmodulin (CaM), but less is known about N-terminal ssMyBP-C and fsMyBP-C. Here, we characterized the conformation of a recombinant N-terminal fragment of ssMyBP-C (ssC1C2) using differential scanning fluorimetry, nuclear magnetic resonance, and molecular modeling. Our studies revealed that ssC1C2 has altered thermal stability in the presence and absence of CaM. We observed that site-specific interaction between CaM and the M-motif of ssC1C2 occurs in a Ca2+-dependent manner. Molecular modeling supported that the M-motif of ssC1C2 likely adopts a three-helix bundle fold comparable to cMyBP-C. Our study provides evidence that ssMyBP-C has overlapping structural determinants, in common with the cardiac isoform, which are important in controlling protein–protein interactions. We shed light on the differential molecular regulation of contractility that exists between skeletal and cardiac muscle. View Full-Text
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Springer, T.I.; Johns, C.W.; Cable, J.; Lin, B.L.; Sadayappan, S.; Finley, N.L. Calcium-Dependent Interaction Occurs between Slow Skeletal Myosin Binding Protein C and Calmodulin. Magnetochemistry 2018, 4, 1.
Springer TI, Johns CW, Cable J, Lin BL, Sadayappan S, Finley NL. Calcium-Dependent Interaction Occurs between Slow Skeletal Myosin Binding Protein C and Calmodulin. Magnetochemistry. 2018; 4(1):1.Chicago/Turabian Style
Springer, Tzvia I.; Johns, Christian W.; Cable, Jana; Lin, Brian L.; Sadayappan, Sakthivel; Finley, Natosha L. 2018. "Calcium-Dependent Interaction Occurs between Slow Skeletal Myosin Binding Protein C and Calmodulin." Magnetochemistry 4, no. 1: 1.
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