Diversified Structural Basis of a Conserved Molecular Mechanism for pH-Dependent Dimerization in Spider Silk N-Terminal Domains
Diversified Structural Basis of a Conserved Molecular Mechanism for pH-Dependent Dimerization in Spider Silk N-Terminal Domains
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DOI：
10.1002/cbic.201500263
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发表时间：
2015-08-17
期刊：
影响因子：
3.2
通讯作者：
Jaudzems, Kristaps
中科院分区：
文献类型：
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作者：
Otikovs, Martins;Chen, Gefei;Jaudzems, Kristaps
蜘蛛丝蛋白从可溶性原液向不溶性纤维的转化涉及 N 端结构域 (NT) 的 pH 依赖性二聚化。这种转化受到严格控制，以防止过早沉淀并能够在管道末端快速形成丝。 Euprosthenops australis 大壶腹蛛丝蛋白 1 的 NT 中介导这一过程的三个谷氨酸残基在蛛丝蛋白中得到了很好的保守。然而，包括 Araneus ventricosus ((Av)MiSp NT) 在内的多个物种的小壶腹蛛丝蛋白 NT 缺乏其中一种谷氨酸。在这里，我们研究了 (Av)MiSp NT 的 pH 依赖性结构变化，表明它使用相同的机制，但涉及非保守的谷氨酸残基。其他 MiSp NT 结构的同源建模表明，它们具有不同的补偿残基。这表明，尽管序列存在差异，NT 依赖于 pH 的二聚化的分子机制在不同的丝类型中是保守的。
Conversion of spider silk proteins from soluble dope to insoluble fibers involves pH-dependent dimerization of the N-terminal domain (NT). This conversion is tightly regulated to prevent premature precipitation and enable rapid silk formation at the end of the duct. Three glutamic acid residues that mediate this process in the NT from Euprosthenops australis major ampullate spidroin 1 are well conserved among spidroins. However, NTs of minor ampullate spidroins from several species, including Araneus ventricosus ((Av)MiSp NT), lack one of the glutamic acids. Here we investigate the pH-dependent structural changes of (Av)MiSp NT, revealing that it uses the same mechanism but involves a non-conserved glutamic acid residue instead. Homology modeling of the structures of other MiSp NTs suggests that these harbor different compensatory residues. This indicates that, despite sequence variations, the molecular mechanism underlying pH-dependent dimerization of NT is conserved among different silk types.