Predicting the transmembrane secondary structure of ligand-gated ion channels
Predicting the transmembrane secondary structure of ligand-gated ion channels
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DOI：
10.1093/protein/15.6.443
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发表时间：
2002-06-01
期刊：
影响因子：
--
通讯作者：
Trudell, JR
中科院分区：
文献类型：
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作者：
Bertaccini, E;Trudell, JR
最近对配体门控离子通道（lgic）的突变分析表明，在其跨膜结构域内可能存在麻醉作用。尽管人们一致认为跨膜结构域是由四个跨膜片段组成的，但这些片段的二级结构尚不清楚。我们利用了10种最先进的生物信息学技术来预测与麻醉作用相关的6个LGIC家族成员的四聚体区域的跨膜拓扑结构。它们是人类形式的GABA α 1受体，甘氨酸α 1受体，5HT3血清素受体，烟碱AChR α 4和α 7受体以及鱼雷nAChR α 1受体。采用的算法有HMMTOP、TMHMM、TMPred、PHDhtm、DAS、TMFinder、SOSUI、TMAP、MEMSAT和TOPPred2。结果预测叠加到使用CLUSTAL W算法创建的六个氨基酸序列的多序列比对上。有一个明确的统计共识，即在实验认为跨越膜的那些区域存在四个α螺旋。10种拓扑预测技术的共识支持了lgic的跨膜亚基是α螺旋的四聚束的假设。
Recent mutational analyses of ligand-gated ion channels (LGICs) have demonstrated a plausible site of anesthetic action within their transmembrane domains. Although there is a consensus that the transmembrane domain is formed from four membrane-spanning segments, the secondary structure of these segments is not known. We utilized 10 state-of-the-art bioinformatics techniques to predict the transmembrane topology of the tetrameric regions within six members of the LGIC family that are relevant to anesthetic action. They are the human forms of the GABA alpha 1 receptor, the glycine alpha 1 receptor, the 5HT3 serotonin receptor, the nicotinic AChR alpha 4 and alpha 7 receptors and the Torpedo nAChR alpha 1 receptor. The algorithms utilized were HMMTOP, TMHMM, TMPred, PHDhtm, DAS, TMFinder, SOSUI, TMAP, MEMSAT and TOPPred2. The resulting predictions were superimposed on to a multiple sequence alignment of the six amino acid sequences created using the CLUSTAL W algorithm. There was a clear statistical consensus for the presence of four alpha helices in those regions experimentally thought to span the membrane. The consensus of 10 topology prediction techniques supports the hypothesis that the transmembrane subunits of the LGICs are tetrameric bundles of alpha helices.