Statistical limits to the identification of ion channel domains by sequence similarity.
Statistical limits to the identification of ion channel domains by sequence similarity.
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DOI：
10.1085/jgp.200509419
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发表时间：
2006-06
期刊：
影响因子：
--
通讯作者：
Aldrich RW
中科院分区：
文献类型：
--
作者：
Fodor AA;Aldrich RW
离子通道功能的研究受到仅少数通道结构可用性的限制。常用的生物信息学技术是基于序列相似性断言感兴趣通道内的结构域与结构已知的参考结构域具有相同的结构。该技术虽然有用，但通常在感兴趣的通道与已知结构的域之间仅有轻微相似之处时使用。在这项研究中，我们利用结构基因组学的最新进展来计算多个离子通道中推定结构域存在的基于序列的概率。我们发现文献中提出的许多领域的存在得到了强有力的支持。例如，真核和原核 CLC 蛋白几乎肯定具有共同的结构。然而，许多提议的域并没有得到很好的支持。特别是，对于 BK 通道的 COOH 末端，我们发现许多文献提出的域，其中基于公共序列的公共结构的断言具有不小的错误概率。
The study of ion channel function is constrained by the availability of structures for only a small number of channels. A commonly used bioinformatics technique is to assert, based on sequence similarity, that a domain within a channel of interest has the same structure as a reference domain for which the structure is known. This technique, while useful, is often employed when there is only a slight similarity between the channel of interest and the domain of known structure. In this study, we exploit recent advances in structural genomics to calculate the sequence-based probability of the presence of putative domains in a number of ion channels. We find strong support for the presence of many domains that have been proposed in the literature. For example, eukaryotic and prokaryotic CLC proteins almost certainly share a common structure. A number of proposed domains, however, are not as well supported. In particular, for the COOH terminus of the BK channel we find a number of literature proposed domains for which the assertion of common structure based on common sequence has a nontrivial probability of error.
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