Localization of the binding site of the C-terminal domain of cardiac myosin-binding protein-C on the myosin rod
Key result
Recombinant C10 bound full-length LMM with a Kd of 3.52 microM and stoichiometry of 1.14, with the binding site localized between residues 1554 and 1581, unaffected by tested HCM mutations.
Population
Recombinant C10 domain of cardiac myosin-binding protein-C (cMyBP-C) and light meromyosin (LMM) fragments
Comparison
Introduction of HCM mutations in LMM, N-terminal… vs Wild-type full-length LMM
Design
Preclinical
Authors
Discussion
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Member takes
Implication
No immediate clinical implications for HCM; leaves open the functional significance of C10-LMM binding in vivo.
Structured PICO
P
Population
Recombinant C10 domain of cardiac myosin-binding protein-C (cMyBP-C) and light meromyosin (LMM) fragments
I
Intervention
Introduction of HCM mutations (A1379T or S1776G) in LMM, N-terminal truncations, and mutation of acidic residue clusters
C
Comparator
Wild-type full-length LMM
O
Outcome
Binding affinity (Kd) and stoichiometry of C10 to LMMsurrogate
The C10 domain of cMyBP-C binds to the LMM portion of the myosin rod between residues 1554 and 1581, and this interaction is not disrupted by specific HCM mutations.
Cite This Study
Flashman et al. (2006) studied Hypertrophic cardiomyopathy. Recombinant C10 binding to LMM was evaluated on Binding affinity (Kd), stoichiometry, and localization of the binding site. Recombinant C10 bound full-length LMM with a Kd of 3.52 microM and stoichiometry of 1.14, with the binding site localized between residues 1554 and 1581, unaffected by tested HCM mutations.