Cardiac actin changes in the actomyosin interface have different effects on myosin duty ratio

• Published in: Biochemistry and cell biology Vol. 96; no. 1; pp. 1 - 31
• Main Authors: Liu, Haidun, Henein, Mary, Anillo, Maria, Dawson, John F
• Format: Journal Article
• Language: English
• Published: Canada Canadian Science Publishing NRC Research Press 01.02.2018
• Subjects: Actin; Actomyosin; Adenosine triphosphatase; Adenosine triphosphate; Binding sites; Biochemistry; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Cardiovascular diseases; Contraction; Cycle ratio; Effects; Heart; Heart diseases; Hypotheses; Mutation; Myocardium; Myosin; Myosin ATPase; Proteins; Sarcomeres; Studies; Ventricle; duty ratio; cardiac actin; mutations; actine cardiaque; actomyosine; actomyosin; hypertrophic cardiomyopathy; facteur de marche; cardiomyopathie hypertrophique
• ISSN: 0829-8211; 1208-6002
• DOI: 10.1139/bcb-2017-0136

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease (CD) that commonly causes an increased size of cardiomyocytes in the left ventricle. The proteins myosin and actin interact in the myocardium to produce contraction through the actomyosin ATPase cycle. The duty ratio (r) of myosin is the proportion of the actomyosin ATPase cycle that myosin is bound to actin and does work. A common hypothesis is that HCM mutations increase contraction in cardiac sarcomeres; however, the available data are not clear on this connection. Based on previous work with human α-cardiac actin (ACTC), we hypothesize that HCM-linked ACTC variants with alterations near the myosin binding site have an increased r, producing more force. Myosin duty ratios using human ACTC variant proteins were calculated with myosin ATPase activity and in-vitro motility data. We found no consistent changes in the duty ratio of the ACTC variants, suggesting that other factors are involved in the development of HCM when ACTC variants are present.