Conserved structural determinants in three-fingered protein domains
Conserved structural determinants in three-fingered protein domains
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DOI：
10.1111/j.1742-4658.2008.06473.x
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发表时间：
2008-06-01
期刊：
影响因子：
5.4
通讯作者：
Menez, Andre
中科院分区：
文献类型：
--
作者：
Galat, Andrzej;Gross, Gregory;Menez, Andre
蛇毒某些成分的三维结构类似于激活素、骨形态发生蛋白和转化生长因子-β受体的胞外结构域，以及Ly6和PlauR基因编码的多种蛋白质。对不同的蛇毒素、与激活素和其他细胞因子结合的受体的不同外区以及Ly6和Plaur家族编码的大量基因产物的序列分析表明，它们彼此之间有很大的差异。TFPD的序列可能由多达六个二硫键组成，其中三个具有相同的高度保守的拓扑结构。这三个二硫键和TFPD C-末端的天冬酰胺残基对于TFPD样折叠是必不可少的。对不同TFPD的三维结构的分析表明，在某些蛇毒中的TFPD和几种细胞受体的胞外区中，三个高度保守的二硫键对TFPD样折叠具有重要的稳定作用，而其余的三个二硫键在一些TFPD的三个手指上施加了特定的几何约束。
The three-dimensional structures of some components of snake venoms forming so-called 'three-fingered protein' domains (TFPDs) are similar to those of the ectodomains of activin, bone morphogenetic protein and transforming growth factor-beta receptors, and to a variety of proteins encoded by the Ly6 and Plaur genes. The analysis of sequences of diverse snake toxins, various ectodomains of the receptors that bind activin and other cytokines, and numerous gene products encoded by the Ly6 and Plaur families of genes has revealed that they differ considerably from each other. The sequences of TFPDs may consist of up to six disulfide bonds, three of which have the same highly conserved topology. These three disulfide bridges and an asparagine residue in the C-terminal part of TFPDs are essential for the TFPD-like fold. Analyses of the three-dimensional structures of diverse TFPDs have revealed that the three highly conserved disulfides impose a major stabilizing contribution to the TFPD-like fold, in both TFPDs contained in some snake venoms and ectodomains of several cellular receptors, whereas the three remaining disulfide bonds impose specific geometrical constraints in the three fingers of some TFPDs.