Peng Junhui, Svetec Nicolas, Molina Henrik, Zhao Li
Laboratory of Evolutionary Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Proteomics Resource Center, The Rockefeller University, New York, NY, USA.
Mol Biol Evol. 2024 Apr 2;41(4). doi: 10.1093/molbev/msae065.
Post-mating responses play a vital role in successful reproduction across diverse species. In fruit flies, sex peptide binds to the sex peptide receptor, triggering a series of post-mating responses. However, the origin of sex peptide receptor predates the emergence of sex peptide. The evolutionary origins of the interactions between sex peptide and sex peptide receptor and the mechanisms by which they interact remain enigmatic. In this study, we used ancestral sequence reconstruction, AlphaFold2 predictions, and molecular dynamics simulations to study sex peptide-sex peptide receptor interactions and their origination. Using AlphaFold2 and long-time molecular dynamics simulations, we predicted the structure and dynamics of sex peptide-sex peptide receptor interactions. We show that sex peptide potentially binds to the ancestral states of Diptera sex peptide receptor. Notably, we found that only a few amino acid changes in sex peptide receptor are sufficient for the formation of sex peptide-sex peptide receptor interactions. Ancestral sequence reconstruction and molecular dynamics simulations further reveal that sex peptide receptor interacts with sex peptide through residues that are mostly involved in the interaction interface of an ancestral ligand, myoinhibitory peptides. We propose a potential mechanism whereby sex peptide-sex peptide receptor interactions arise from the preexisting myoinhibitory peptides-sex peptide receptor interface as well as early chance events both inside and outside the preexisting interface that created novel sex peptide-specific sex peptide-sex peptide receptor interactions. Our findings provide new insights into the origin and evolution of sex peptide-sex peptide receptor interactions and their relationship with myoinhibitory peptides-sex peptide receptor interactions.
交配后反应在不同物种的成功繁殖中起着至关重要的作用。在果蝇中，性肽与性肽受体结合，引发一系列交配后反应。然而，性肽受体的起源早于性肽的出现。性肽与性肽受体之间相互作用的进化起源及其相互作用机制仍然是个谜。在本研究中，我们使用祖先序列重建、AlphaFold2预测和分子动力学模拟来研究性肽-性肽受体相互作用及其起源。利用AlphaFold2和长时间分子动力学模拟，我们预测了性肽-性肽受体相互作用的结构和动力学。我们发现性肽可能与双翅目性肽受体的祖先状态结合。值得注意的是，我们发现性肽受体中只有少数氨基酸变化就足以形成性肽-性肽受体相互作用。祖先序列重建和分子动力学模拟进一步揭示，性肽受体通过主要参与祖先配体肌抑制肽相互作用界面的残基与性肽相互作用。我们提出了一种潜在机制，即性肽-性肽受体相互作用源于预先存在的肌抑制肽-性肽受体界面以及该预先存在界面内外的早期偶然事件，这些事件创造了新的性肽特异性性肽-性肽受体相互作用。我们的研究结果为性肽-性肽受体相互作用的起源和进化及其与肌抑制肽-性肽受体相互作用的关系提供了新的见解。
