期刊
BIOCHEMICAL JOURNAL
卷 473, 期 -, 页码 2485-2493出版社
PORTLAND PRESS LTD
DOI: 10.1042/BCJ20160421
关键词
actin; alpha-actinin; cardiomyocytes; crystal structure; familial hypertrophic cardiomyopathy; imaging
资金
- Biotechnology and Biological Sciences Research Council [BB/I007423/1]
- Welcome Trust [WT094232]
- Biotechnology and Biological Sciences Research Council White Rose DTP PhD studentship [BB/J014443/1]
- BBSRC [BB/I007423/1, BB/L015056/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1501686, BB/L015056/1, BB/I007423/1] Funding Source: researchfish
alpha-Actinin-2 (ACTN2) is the only muscle isoform of alpha-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients, A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain (ABD) of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localization and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据