The structure of isolated cardiac myosin thick filaments from cardiac myosin binding protein-C knockout mice
The structure of isolated cardiac myosin thick filaments from cardiac myosin binding protein-C knockout mice
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DOI：
10.1529/biophysj.107.115899
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Harrist, Samantha P.
中科院分区：
文献类型：
--
作者：
Kensler, Robert W.;Harrist, Samantha P.
粗丝相关蛋白心肌肌球蛋白结合蛋白-C (cMyBP-C) 的突变是家族性肥厚型心肌病的主要原因。尽管cMyBP-C被认为在心肌收缩中发挥结构和调节作用，但有关该蛋白质在粗丝稳定性和维持肌球蛋白跨桥有序螺旋排列中的作用的详细信息是有限的。为了解决这些问题，我们将从含有 cMyBP-C (cMyBP-C+/+) 的野生型小鼠心脏中分离出的肌球蛋白粗丝结构与缺乏该蛋白的 cMyBP-C 敲除小鼠 (cMyBP-C-/-) 的结构进行了比较。来自缺乏 cMyBP-C 的敲除小鼠心脏的细丝是稳定的，并且在长度和外观上与来自含有 cMyBP-C 的野生型小鼠心脏的细丝相似。野生型和许多 cMyBP-C-/- 丝都显示出独特的 43 nm 周期性。电子显微镜图像的傅立叶变换通常显示到第六层线的螺旋层线，证实了两组细丝中的交叉桥的有序排列。然而，“禁止的”经向反射被认为源自野生型丝中螺旋对称性的扰动，在 cMyBP-C-/- 心肌粗丝的变换中较弱或不存在。此外，在没有cMyBP-C的情况下，跨桥阵列更容易出现紊乱。
Mutations in the thick filament associated protein cardiac myosin binding protein-C (cMyBP-C) area major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C is thought to play both a structural and a regulatory role in the contraction of cardiac muscle, detailed information about the role of this protein in stability of the thick filament and maintenance of the ordered helical arrangement of the myosin cross-bridges is limited. To address these questions, the structure of myosin thick filaments isolated from the hearts of wild-type mice containing cMyBP-C (cMyBP-C+/+) were compared to those of cMyBP-C knockout mice lacking this protein (cMyBp-C-/-). The filaments from the knockout mice hearts lacking cMyBP-C are stable and similar in length and appearance to filaments from the wild-type mice hearts containing cMyBP-C. Both wild-type and many of the cMyBP-C-/- filaments display a distinct 43 nm periodicity. Fourier transforms of electron microscope images typically show helical layer lines to the sixth layer line, confirming the well-ordered arrangement of the cross-bridges in both sets of filaments. However, the "forbidden" meridional reflections, thought to derive from a perturbation from helical symmetry in the wild-type filament, are weaker or absent in the transforms of the cMyBP-C-/- myocardial thick filaments. In addition, the cross-bridge array in the absence of cMyBP-C appears more easily disordered.