Architecture of the thin filament-Z-line junction: lessons from nebulette and nebulin homologies.
Architecture of the thin filament-Z-line junction: lessons from nebulette and nebulin homologies.
复制标题
细丝-Z 线连接的结构：星云和星云蛋白同源性的教训。
DOI：
10.1023/a:1005697226465
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发表时间：
2000
影响因子：
2.7
通讯作者：
Wang,K
中科院分区：
文献类型：
--
作者：
Moncman,CL;Wang,K
Nebulette和nebulin是与心脏和骨骼肌肌节z线相关的同源蛋白。尽管这些蛋白具有70%的序列同源性和相同的结构域布局，但nebulette的大小只有星云蛋白的十分之一。为了从z线结构上定义这些蛋白质的重要结构特征，我们分析了来自不同物种和发育阶段的nebulette和nebulin的主要结构。对这两种蛋白质的35个残基星云样模块的比对表明，在所分析的6种蛋白质中，单个模块具有30-90%的同源性。此外，该分析还表明，在许多区域，这六种蛋白质的同一性高达75%。这些区域可能是横纹肌中z线组装和功能的重要信号。值得注意的是，大多数高度同一性的区域也与一致的磷酸化位点一致。为了评估nebulette是否像nebulin一样表现出组织特异性和发育特异性多态性，进行了一系列免疫印迹试验。这些数据表明，来自心脏不同部位的星云大小相同。胚胎心肌和成人心肌的nebulette的比较也表明，这种蛋白质的大小似乎不随发育阶段而变化。与在nebulette初级结构中发现的大量一致的磷酸化位点一致，我们发现nebulette在心肌中的丝氨酸和苏氨酸残基上被磷酸化。这些数据和序列分析是根据现有的z线体系结构模型进行讨论的。
Nebulette and nebulin are homologous proteins associated with the Z-lines of cardiac and skeletal muscle sarcomeres. Although these proteins share ∼70% sequence homology and an identical domain layout, nebulette is one-tenth the size of nebulin. To define structurally important features of these proteins in terms of the Z-line architecture, we have analyzed the primary structure of nebulette and nebulin from a variety of species and developmental stages. Alignment of the 35 residue nebulin-like modules from both proteins demonstrates that the individual modules share 30–90% homology across the six proteins analyzed. In addition, this analysis demonstrates a number of areas in which the identity across the six proteins is as high as 75%. These areas may be important signals for Z-line assembly and function in the striated muscles. Significantly, most of the areas of high identity also coincide with consensus phosphorylation sites. To evaluate if nebulette, like nebulin, exhibits tissue-specific and developmental specific polymorphism, a series of immunoblot assays were performed. These data demonstrate that nebulettes from different portions of the heart are the same size. Comparison of nebulette from embryonic and adult cardiac muscle also demonstrates that this protein does not appear to vary in size with developmental stage. Consistent with the large number of consensus phosphorylation sites identified in the nebulette primary structure, we find that nebulette is phosphorylated in the cardiac muscle at serine and threonine residues. These data and sequence analyses are discussed in terms of current models for Z-line architecture.