Duality in disease: How two amino acid substitutions at actin residue 312 result in opposing forms of cardiomyopathy.

ABSTRACT: Two common types of cardiovascular disease are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) which occur from changes to sarcomere contractile mechanisms and activity. Actin amino acid substitutions R312C and R312H have been found in HCM and DCM patients, respectively. Previously, we observed that R312C/H variants display both hyperactivity and hypoactivity in vitro, contradicting traditional characterizations of HCM- and DCM-causing variants. Here, we further characterized R312C/H actin variants in vitro and conducted in silico modeling to better understand the mechanisms differentiating HCM and DCM. Our results suggest that R312C/H substitutions cause structural changes that differentially impact actomyosin activity. A gradient of altered interactions with regulatory

SUBMITTER: Steffensen KE 

PROVIDER: S-EPMC11652881 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature