Characterization of Familial Hypertrophic Cardiomyopathy on Myosin Essential Light Chain Mutation (A57G)

• Main Authors: none none, 李亭儀
• Other Authors: Hui-chun Li
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/45887447354378898006

碩士 === 慈濟大學 === 醫學研究所 === 96 === Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy, myofibrillar disarray, and sudden cardiac death. It is caused by missense mutations in various genes that code for sarcomereic proteins such as myosin. Myosin is the major protein in muscle responsible for force generation. Human cardiac myosin is a dimmer each consists of 240KDa heavy chain, a 24KDa essential light chain and a 17KDa regulatory light chain. Three ELC mutations were identified from FHC patients. We hypothesize that these mutations would affect the structure and function of myosin. The aim of this project is to investigate the effect of FHC mutations of ELC on myosin. Circular dichroism spectra showed that both wild type ELC and A57G mutant had similar secondary structure content. Wild type or mutant ELC is labeled with fluorescent probe and exchanged onto isolated cardiac myosin for structural and functional assays. Fluorescence spectroscopy is used to characterize the structural changes to each of the four ATPase intermediate stages of exchanged myosin. Actin-activated myosin ATPase activity is used as a functional assay.