Walcott Sam, Docken Steffen, Harris Samantha P
Department of Mathematics, University of California at Davis, Davis, California.
Department of Mathematics, University of California at Davis, Davis, California.
Biophys J. 2015 Jan 6;108(1):10-3. doi: 10.1016/j.bpj.2014.11.1852.
Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart disease, its role in muscle contraction is not well understood. A mechanism remains elusive partly because the protein can have multiple effects, such as dual biphasic activation and inhibition observed in actin motility assays. Here we develop a mathematical model for the interaction of cMyBP-C with the contractile proteins actin and myosin and the regulatory protein tropomyosin. We use this model to show that a drag-activation-competition mechanism accurately describes actin motility measurements, while models lacking either drag or competition do not. These results suggest that complex effects can arise simply from cMyBP-C binding to actin.
尽管心肌肌球蛋白结合蛋白C（cMyBP-C）的突变会引发心脏病，但其在肌肉收缩中的作用尚未得到充分理解。一种机制仍然难以捉摸，部分原因是该蛋白可能具有多种效应，例如在肌动蛋白运动测定中观察到的双相激活和抑制。在这里，我们建立了一个关于cMyBP-C与收缩蛋白肌动蛋白和肌球蛋白以及调节蛋白原肌球蛋白相互作用的数学模型。我们使用这个模型表明，一种拖动-激活-竞争机制能够准确描述肌动蛋白运动测量结果，而缺乏拖动或竞争的模型则不能。这些结果表明，cMyBP-C与肌动蛋白的结合可能会产生复杂的效应。
