Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
PLoS One. 2010 Oct 6;5(10):e12827. doi: 10.1371/journal.pone.0012827.
Voltage-gated and ligand-gated ion channels are used in eukaryotic organisms for the purpose of electrochemical signaling. There are prokaryotic homologues to major eukaryotic channels of these sorts, including voltage-gated sodium, potassium, and calcium channels, Ach-receptor and glutamate-receptor channels. The prokaryotic homologues have been less well characterized functionally than their eukaryotic counterparts. In this study we identify likely prokaryotic functional counterparts of eukaryotic glutamate receptor channels by comprehensive analysis of the prokaryotic sequences in the context of known functional domains present in the eukaryotic members of this family. In particular, we searched the nonredundant protein database for all proteins containing the following motif: the two sections of the extracellular glutamate binding domain flanking two transmembrane helices. We discovered 100 prokaryotic sequences containing this motif, with a wide variety of functional annotations. Two groups within this family have the same topology as eukaryotic glutamate receptor channels. Group 1 has a potassium-like selectivity filter. Group 2 is most closely related to eukaryotic glutamate receptor channels. We present analysis of the functional domain architecture for the group of 100, a putative phylogenetic tree, comparison of the protein phylogeny with the corresponding species phylogeny, consideration of the distribution of these proteins among classes of prokaryotes, and orthologous relationships between prokaryotic and human glutamate receptor channels. We introduce a construct called the Evolutionary Domain Network, which represents a putative pathway of domain rearrangements underlying the domain composition of present channels. We believe that scientists interested in ion channels in general, and ligand-gated ion channels in particular, will be interested in this work. The work should also be of interest to bioinformatics researchers who are interested in the use of functional domain-based analysis in evolutionary and functional discovery.
电压门控和配体门控离子通道在真核生物中用于电化学信号传递。原核生物中存在与这些通道主要的真核生物同源物，包括电压门控钠离子、钾离子和钙离子通道、Ach 受体和谷氨酸受体通道。与真核生物相比，原核生物的同源物在功能上的特征描述还不够完善。在这项研究中，我们通过对真核生物家族成员中存在的已知功能域的全面分析，确定了真核谷氨酸受体通道的可能原核功能对应物。特别是，我们在非冗余蛋白质数据库中搜索了所有包含以下模体的蛋白质：两个侧翼两个跨膜螺旋的细胞外谷氨酸结合域的两个部分。我们发现了 100 个含有这种模体的原核序列，它们具有广泛的功能注释。该家族中有两个亚组具有与真核谷氨酸受体通道相同的拓扑结构。第 1 组具有类似于钾离子的选择性过滤器。第 2 组与真核谷氨酸受体通道最为密切相关。我们对这 100 个序列的功能域结构进行了分析，提出了一个假设的系统发育树，比较了蛋白质系统发育与相应物种系统发育之间的关系，考虑了这些蛋白质在原核生物类群中的分布，以及原核生物和人类谷氨酸受体通道之间的同源关系。我们引入了一种称为进化域网络的结构，它代表了目前通道的域组成背后的域重排的潜在途径。我们相信，对离子通道特别是配体门控离子通道感兴趣的科学家会对这项工作感兴趣。这项工作也应该引起对使用基于功能域的分析进行进化和功能发现感兴趣的生物信息学研究人员的关注。
