Introduction: The first vertebrates were jawless fish, or Agnatha, whose evolution diverged into jawed fish, or Gnathostomes, around 550 million years ago. Methods: In this study, we investigated β PFT proteins' evolutionary divergence of lamprey immune protein from Agnatha, reportedly possessing anti-cancer activity, into Dln1 protein from Gnathostomes. Both proteins showed structural and functional divergence, and shared evolutionary origin. Primary, secondary and tertiary sequences were compared to discover functional domains and conserved motifs in order to study the evolution of these two proteins. The structural and functional information relevant to evolutionary divergence was revealed using hydrophobic cluster analysis. Results: The findings demonstrate that two membrane proteins with only a small degree of sequence identity can have remarkably similar hydropathy profiles, pointing towards conserved and similar global structures. When facing the lipid bilayer or lining the pore lumen, the two proteins' aerolysin domains' corresponding residues displayed a similar and largely conserved pattern. Aerolysin-like proteins from different species can be identified using a fingerprint created by PIPSA analysis of the pore-forming protein. Conclusion: We were able to fully understand the mechanism of action during pore formation through structural studies of these proteins.

中文翻译：

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基于β成孔蛋白的颌口动物与无颌动物的进化分歧

简介：最早的脊椎动物是无颌鱼（Agnatha），它在大约 5.5 亿年前进化为有颌鱼（Gnathostomes）。方法：在本研究中，我们研究了β PFT 蛋白从无颌类七鳃鳗免疫蛋白（据报道具有抗癌活性）到颚口类动物 Dln1 蛋白的进化差异。两种蛋白质都表现出结构和功能上的差异，并且具有共同的进化起源。比较一级、二级和三级序列以发现功能域和保守基序，从而研究这两种蛋白质的进化。使用疏水聚类分析揭示了与进化分歧相关的结构和功能信息。结果：研究结果表明，仅具有少量序列同一性的两种膜蛋白可以具有非常相似的亲水特性，这表明它们具有保守且相似的整体结构。当面对脂质双层或衬在孔腔时，两种蛋白质的气溶素结构域的相应残基表现出相似且很大程度上保守的模式。来自不同物种的气溶素样蛋白可以通过对成孔蛋白进行 PIPSA 分析而产生的指纹来识别。结论：通过对这些蛋白质的结构研究，我们能够充分了解孔形成过程中的作用机制。