Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 550, Issue -, Pages 28-32Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2014.04.003
Keywords
Cardiac actin; Myosin binding protein-C; Heart disease; Cardiomyopathy
Categories
Funding
- NIH [HL080367]
- Heart and Stroke Foundation of Canada [NA6469]
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The two genes most commonly associated with mutations linked to hypertrophic or dilated cardiomyopathies are beta-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 K-d 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. (C) 2014 Elsevier Inc. All rights reserved.
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