Abstract
Mutations in the cardiac actin gene (ACTC1) are associated with the development of hypertrophic cardiomyopathy (HCM). To date, 12 different ACTC1 mutations have been discovered in patients with HCM. Given the high degree of sequence conservation of actin proteins and the range of protein–protein interactions actin participates in, mutations in cardiac actin leading to HCM are particularly interesting. Here, we suggest the classification of ACTC1 mutations based on the location of the resulting amino acid change in actin into three main groups: (1) those affecting only the binding site of the myosin molecular motor, termed M-class mutations, (2) those affecting only the binding site of the tropomyosin (Tm) regulatory protein, designated T-class mutations, and (3) those affecting both the myosin- and Tm-binding sites, called MT-class mutations. To understand the precise pathogenesis of cardiac actin mutations and develop treatments specific to the molecular cause of disease, we need to integrate rapidly growing structural information with studies of regulated actomyosin systems.
Highlights
Cardiovascular disease is the leading cause of death worldwide, and puts a strain on the global economy, costing the Canadian economy >$22 billion annually (Gaziano, 2007; Smith, 2009)
In this mini-review, we propose classification of the hypertrophic cardiomyopathy (HCM)-linked ACTC1 mutations based on the location of the amino acid changes in ACTC, and their proposed protein interactions
Understanding the mechanistic cause of HCM has become increasingly important in research, with experiments moving beyond basic biochemical properties to investigate altered protein–protein interactions
Summary
Reviewed by: Margaret Westfall, University of Michigan, United States Charles Redwood, University of Oxford, United Kingdom Beata M. University of Illinois at Chicago, United States. Classifying Cardiac Actin Mutations Associated With Hypertrophic Cardiomyopathy. Mutations in the cardiac actin gene (ACTC1) are associated with the development of hypertrophic cardiomyopathy (HCM). We suggest the classification of ACTC1 mutations based on the location of the resulting amino acid change in actin into three main groups: (1) those affecting only the binding site of the myosin molecular motor, termed M-class mutations, (2) those affecting only the binding site of the tropomyosin (Tm) regulatory protein, designated T-class mutations, and (3) those affecting both the myosin- and Tm-binding sites, called MT-class mutations.
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