Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Immunogenetics. 2019 Jan;71(1):61-69. doi: 10.1007/s00251-018-1086-y. Epub 2018 Oct 2.
Defensins are small, cysteine-rich, cationic antimicrobial peptides, serving as effectors of the innate immune system and modulators of the adaptive immune system. They extensively exist in multicellular organisms and are divided into cis and trans according to their disulfide bridge connectivity patterns. It has been proposed that these two types of defensins convergently originated from different ancestors. Here, we report the discovery of a structural signature involved in the formation of the cysteine-stabilized α-helix/β-sheet (CSαβ) fold of the cis-defensins in some trans-β-defensins, with only one amino acid indel (CXC vs. CC. C, cysteine; X, any amino acid). The indel of the X residue in the structural signature provides a possible explanation as to why cis- and trans-defensins possess different folds and connectivity patterns of disulfide bridges formed in evolution. Although our attempt to convert the structure type of a present-day trans-defensin with the X residue deleted was unsuccessful due to the low solubility of the synthetic peptide, a combination of data from structural signature, function, and phylogenetic distribution suggests that these defensins may have descended from a common ancestor. In this evolutionary scenario, we propose that a progenitor cis-scaffold might gradually evolve into a trans-defensin after deleting the X residue in specific lineages. This proposal adds a new dimension to more deeply studying the evolutionary relationship of defensins with different folds and of other distantly related proteins.
防御素是富含半胱氨酸的阳离子抗菌肽，是先天免疫系统的效应物和适应性免疫系统的调节剂。它们广泛存在于多细胞生物中，根据其二硫键连接模式分为顺式和反式。有人提出，这两种类型的防御素是从不同的祖先中趋同进化而来的。在这里，我们报告了在一些反式-β防御素中发现了一种结构特征，该特征参与了顺式防御素中半胱氨酸稳定的α-螺旋/β-折叠（CSαβ）折叠的形成，其结构特征中仅存在一个氨基酸插入/缺失（CXC 与 CC。C，半胱氨酸；X，任何氨基酸）。结构特征中 X 残基的插入/缺失为顺式和反式防御素在进化中形成不同折叠和二硫键连接模式提供了一个可能的解释。尽管我们试图通过删除 X 残基来改变目前具有 X 残基的反式防御素的结构类型，但由于合成肽的溶解度较低，尝试失败了，但结构特征、功能和系统发生分布的数据结合表明，这些防御素可能来自一个共同的祖先。在这种进化情景中，我们提出，在前体顺式支架中，在特定谱系中删除 X 残基后，可能会逐渐进化为反式防御素。这一假设为更深入地研究不同折叠的防御素以及其他远缘相关蛋白质的进化关系增添了新的维度。
