Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac α-tropomyosin.

Familial hypertrophic cardiomyopathy related E180G mutation increases flexibility of human cardiac α-tropomyosin.
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家族性肥厚性心肌病相关的E180G突变增加了人类心脏α-胶质素的柔韧性。

DOI:
10.1016/j.febslet.2012.08.005
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发表时间:
2012-09-21
期刊:
影响因子:
3.5
通讯作者:
Chase PB
Chase PB
中科院分区:
生物学3区
文献类型:
--
作者:
Loong CK;Zhou HX;Chase PB

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α-原肌球蛋白(αTm)是Ca ~(2+)调节心肌收缩的核心。家族性肥厚型心肌病突变αTm E180 G在功能测定中增强Ca 2+敏感性为了研究分子基础,我们通过直接探针原子力显微镜对人心脏αTm E180 G的单分子进行成像。沿沿着分子轮廓的正切角的分析产生了对应于与野生型相比柔性增加约35%的持久长度。通过拟合蠕虫状链模型的端到端长度分布,证实了突变体的灵活性增加。这种灵活性的显著增加可以显著影响心脏收缩的收缩期和可能的舒张期,最终导致肥大。
α-tropomyosin (αTm) is central to Ca2+-regulation of cardiac muscle contraction. The familial hypertrophic cardiomyopathy mutation αTm E180G enhances Ca2+-sensitivity in functional assays. To investigate the molecular basis, we imaged single molecules of human cardiac αTm E180G by direct probe atomic force microscopy. Analyses of tangent angles along molecular contours yielded persistence length corresponding to ~35% increase in flexibility compared to wild-type. Increased flexibility of the mutant was confirmed by fitting end-to-end length distributions to the worm-like chain model. This marked increase in flexibility can significantly impact systolic and possibly diastolic phases of cardiac contraction, ultimately leading to hypertrophy.
DOI: 10.3389/fphys.2012.00080
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