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首页> 外文期刊>Biochimica et biophysica acta. Biomembranes >Crucial motifs and residues in the extracellular loops influence the formation and specificity of connexin docking
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Crucial motifs and residues in the extracellular loops influence the formation and specificity of connexin docking

机译：细胞外环循环中的关键主题和残留物影响Connexin对接的形成和特异性

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Abstract Most of the early studies on gap junction (GJ) channel function and docking compatibility were on rodent connexins, while recent research on GJ channels gradually shifted from rodent to human connexins largely due to the fact that mutations in many human connexin genes are found to associate with inherited human diseases. The studies on human connexins have revealed some key differences from those found in rodents, calling for a comprehensive characterization of human GJ channels. Functional studies revealed that docking and formation of functional GJ channels between two hemichannels are possible only between docking-compatible connexins. Two groups of docking-compatible rodent connexins have been identified. Compatibility is believed to be due to their amino acid residue differences at the extracellular loop domains (E1 and E2). Sequence alignment of the E1 and E2 domains of all connexins known to make GJs revealed that they are highly conserved and show high sequence identity with human Cx26, which is the only connexin with near atomic resolution GJ structure. We hypothesize that different connexins have a similar structure as that of Cx26 at the E1 and E2 domains and use the corresponding residues in their E1 and E2 domains for docking. Based on the Cx26 GJ structure and sequence analysis of well-studied connexins, we propose that the E1-E1 docking interactions are staggered with each E1 interacting with two E1s on the docked connexon. The putative E1 docking residues are conserved in both docking-compatible and -incompatible connexins, indicating that E1 does not likely serve a role in docking compatibility. However, in the case of E2-E2 docking interactions, the putative docking residues are only conserved within the docking-compatible connexins, suggesting the E2 is likely to serve the function of docking compatibility. Docking compatibility studies on human connexins have attracted a lot of attention due to the fact that putative docking residues are mutational hotspots for several connexin-linked human diseases. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Highlights ? Human connexins differ from those of rodent. ? E1 is highly conserved and likely forms staggered docking interaction. ? E2, but not E1, shows conserved sequence within docking compatible connexins. ? Hydrogen bonds and hydrophobic interactions play a role in gap junction docking.
机译：摘要关于间隙交界（GJ）通道功能和对接兼容性的大多数早期研究都在啮齿动物Connexins上，而最近关于GJ频道的研究逐渐从啮齿动物转移到人体连接蛋白，这主要是因为发现许多人concexin基因中的突变是突变与遗传的人类疾病相关联。对人concexins的研究揭示了啮齿动物中发现的一些关键差异，呼吁综合表征人类GJ频道。功能研究表明，在对接相容的Connexins之间只有两个血管箱之间的功能性GJ通道的对接和形成是可能的。已经确定了两组对接啮合的啮齿动物Connexins。相容性被认为是由于它们在细胞外环域（E1和E2）处的氨基酸残基差异。所有已知GJ的E1和E2结构域的序列比对显示它们具有高度保守的，并且具有人CX26的高序列同一性，这是近几个近原子分辨率GJ结构的Connexin。我们假设不同的Connectins具有与E1和E2结构域的CX26相似的结构，并使用其E1和E2结构域中的相应残留物进行对接。基于CX26 GJ结构和良好研究的Connexins的序列分析，我们提出了E1-E1对接相互作用，每个E1与对接连接的两个E1s相互作用交错。推定的E1对接残留物在对接兼容的和-INCOMPATIble Connexins中保存，表明E1不太可能在对接兼容性方面发挥作用。然而，在E2-E2对接相互作用的情况下，推定的对接残留物仅在对接兼容的连接内部保存，建议E2可能有助于对接兼容性的功能。对人Connexins的兼容性研究由于推定的对接残留物是几种Conneclexin关联的人类疾病的突变热点，因此引起了很多关注。本文是题为的特殊问题的一部分：Jean Claude Herve编辑的Gap Junction蛋白。强调 ？人的Connexins与啮齿动物的Connectins不同。还E1高度保守，可能形成交错的对接互动。还E2，但不是E1，在对接的连接内容下显示保守的序列。还氢键和疏水性相互作用在间隙交叉对接中发挥作用。

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