The CH-domain of calponin does not determine the modes of calponin binding to F-actin
The CH-domain of calponin does not determine the modes of calponin binding to F-actin
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DOI：
10.1016/j.jmb.2006.03.044
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发表时间：
2006-06-02
影响因子：
5.6
通讯作者：
Egelman, Edward H.
中科院分区：
文献类型：
--
作者：
Galkin, Vitold E.;Orlova, Albina;Egelman, Edward H.
已经观察到许多肌动蛋白结合蛋白具有模块结构。最丰富的模块之一是钙调蛋白同源性（CH）结构域，其在蛋白质中作为串联重复发现，所述串联重复交联肌动蛋白丝（如fimplatin、血影蛋白和α-辅肌动蛋白）或将肌动蛋白细胞骨架连接到中间丝（如plectin）。在蛋白质中，如epa-calponin，IQGAP 1和Scp 1，存在一个单一的CH结构域，但这个结构域是否与肌动蛋白丝结合存在争议。以前的三维重建的钙调蛋白-F-肌动蛋白复合物的结论是，可视化的部分钙调蛋白结合到肌动蛋白属于其氨基末端同源（CH）域。我们表明，使用缺乏CH-结构域的钙调蛋白片段，该结构域是不绑定到F-肌动蛋白，不能定位钙调蛋白的F-肌动蛋白的假设。此外，使用分类方法，我们显示了多种合作模式的结合的钙调蛋白F-肌动蛋白，类似于已观察到的其他肌动蛋白结合蛋白，如原肌球蛋白和cofilin。我们的研究结果表明，在许多其他肌动蛋白结合蛋白中发现的结构保守的CH结构域的形式和功能已经分化。这对于从结构保守结构域的存在推断功能具有广泛的意义。(c)2006爱思唯尔有限公司保留所有权利。
Many actin-binding proteins have been observed to have a modular architecture. One of the most abundant modules is the calponin-homology (CH) domain, found as tandem repeats in proteins that cross-link actin filaments (such as fimbrin, spectrin and a-actinin) or link the actin cytoskeleton to intermediate filaments (such as plectin). In proteins such as the eponymous calponin, IQGAP1, and Scp1, a single CH-domain exists, but there has been some controversy over whether this domain binds to actin filaments. A previous three-dimensional reconstruction of the calponin-F-actin complex has led to the conclusion that the visualized portion of calponin bound to actin belongs to its amino-terminal homology (CH) domain. We show, using a calponin fragment lacking the CH-domain, that this domain is not bound to F-actin, and cannot be positioning calponin on F-actin as hypothesized. Further, using classification methods, we show a multiplicity in cooperative modes of binding of calponin to F-actin, similar to what has been observed for other actin-binding proteins such as tropomyosin and cofilin. Our results suggest that the form and function of the structurally conserved CH-domain found in many other actin-binding proteins have diverged. This has broad implications for inferring function from the presence of structurally conserved domains. (c) 2006 Elsevier Ltd. All rights reserved.