Altered interactions between cardiac myosin binding protein-c and α-cardiac actin variants associated with cardiomyopathies
Copyright policy )Altered interactions between cardiac myosin binding protein-c and α-cardiac actin variants associated with cardiomyopathies
The two genes most commonly associated with mutations linked to hypertrophic or dilated cardiomyopathies are β-myosin and cardiac myosin binding protein-C (cMyBP-C). Both of these proteins interact with cardiac actin (ACTC). Currently there are 16 ACTC variants that have been found in patients with HCM or DCM. While some of these ACTC variants exhibit protein instability or polymerization-deficiencies that might contribute to the development of disease, other changes could cause changes in protein-protein interactions between sarcomere proteins and ACTC. To test the hypothesis that changes in ACTC disrupt interactions with cMyBP-C, we examined the interactions between seven ACTC variants and the N-terminal C0C2 fragment of cMyBP-C. We found there was a significant decrease in binding affinity (increase in Kd values) for the A331P and Y166C variants of ACTC. These results suggest that a change in the ability of cMyBP-C to bind actin filaments containing these ACTC protein variants might contribute to the development of disease. These results also provide clues regarding the binding site of the C0C2 fragment of cMyBP-C on F-actin.
- University of California, Irvine United States
- University of Guelph Canada
- University of California, San Francisco United States
- University of Arizona United States
Cardiomyopathy, Dilated, Sarcomeres, Protein Structure, Biochemistry & Molecular Biology, Cardiomyopathy, 610, Gene Expression, Heart disease, Cardiovascular, Ventricular Myosins, Rare Diseases, 616, Dilated, Genetics, 2.1 Biological and endogenous factors, Humans, Binding Sites, Cardiac actin, Myocardium, Myosin binding protein-C, Biological Sciences, Cardiomyopathy, Hypertrophic, Actins, Recombinant Proteins, Protein Structure, Tertiary, Actin Cytoskeleton, Kinetics, Heart Disease, Hypertrophic, Biochemistry and cell biology, Biochemistry and Cell Biology, Carrier Proteins, Tertiary, Protein Binding
Cardiomyopathy, Dilated, Sarcomeres, Protein Structure, Biochemistry & Molecular Biology, Cardiomyopathy, 610, Gene Expression, Heart disease, Cardiovascular, Ventricular Myosins, Rare Diseases, 616, Dilated, Genetics, 2.1 Biological and endogenous factors, Humans, Binding Sites, Cardiac actin, Myocardium, Myosin binding protein-C, Biological Sciences, Cardiomyopathy, Hypertrophic, Actins, Recombinant Proteins, Protein Structure, Tertiary, Actin Cytoskeleton, Kinetics, Heart Disease, Hypertrophic, Biochemistry and cell biology, Biochemistry and Cell Biology, Carrier Proteins, Tertiary, Protein Binding
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