Kinetic properties and small-molecule inhibition of human myosin-6
Kinetic properties and small-molecule inhibition of human myosin-6
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DOI：
10.1016/j.febslet.2012.07.014
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发表时间：
2012-09-21
期刊：
影响因子：
3.5
通讯作者：
Manstein, Dietmar J.
中科院分区：
文献类型：
--
作者：
Heissler, Sarah M.;Selvadurai, Jayashankar;Manstein, Dietmar J.
肌凝蛋白-6是一种基于肌动蛋白的运动蛋白，它将货物移动到肌动蛋白丝的负端。编码肌球蛋白-6重链的基因突变和细胞中该蛋白丰度的变化与肥厚性心肌病、神经退行性疾病和癌症有关。在这里，我们详细描述了人肌球蛋白-6运动结构域的动力学特征，描述了2,4,6-三碘酚对肌球蛋白-6与f -肌动蛋白和核苷酸相互作用的影响，并展示了药物的添加如何减少在组成分泌过程中质膜上肌球蛋白-6依赖性囊泡融合事件的数量。(C) 2012年欧洲生化学会联合会。Elsevier B.V.版权所有。
Myosin-6 is an actin-based motor protein that moves its cargo towards the minus-end of actin filaments. Mutations in the gene encoding the myosin-6 heavy chain and changes in the cellular abundance of the protein have been linked to hypertrophic cardiomyopathy, neurodegenerative diseases, and cancer. Here, we present a detailed kinetic characterization of the human myosin-6 motor domain, describe the effect of 2,4,6-triiodophenol on the interaction of myosin-6 with F-actin and nucleotides, and show how addition of the drug reduces the number of myosin-6-dependent vesicle fusion events at the plasma membrane during constitutive secretion. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.