Urdiciain Alejandro, Madej Thomas, Wang Jiyao, Song James, Erausquin Elena, Youkharibache Philippe, López-Sagaseta Jacinto
Unit of Protein Crystallography and Structural Immunology, Navarrabiomed, 31008, Navarra, Spain.
Public University of Navarra (UPNA), Pamplona, 31008, Navarra, Spain.
Commun Biol. 2025 Mar 20;8(1):463. doi: 10.1038/s42003-025-07830-5.
Understanding the ancestral Ig domain's molecular structure and tracing the evolution of Ig-like proteins are fundamental components missing from our comprehension of their evolutionary trajectory and function. We have determined high-resolution structures of two Ig-like proteins from the evolutionary most ancestral phylum, Porifera. The structures reveal N-terminal Ig-like domains with an unconventional configuration of features that set them apart from canonical Ig domains. These findings prompted us to call this novel domain as Ig "Early Variable" (EV)-set. Remarkably, the EV-sets are linked to C1-set domains. To the best of our knowledge, the C1-set has not been previously reported in non-vertebrates. The IgV and IgC1 tandems and their combination into functional Ig-like receptors are part of the adaptive immune system in higher vertebrates, which allows for highly specific immune responses. By unveiling important clues into the molecular configuration of ancestral Ig domains, these findings challenge and expand our understanding of how immunity has evolved within its current landscape.
了解祖先免疫球蛋白（Ig）结构域的分子结构并追踪Ig样蛋白的进化，是我们在理解其进化轨迹和功能方面所缺失的基本要素。我们已经确定了来自进化上最原始的门——多孔动物门的两种Ig样蛋白的高分辨率结构。这些结构揭示了N端Ig样结构域具有非常规的特征构型，使其与典型的Ig结构域不同。这些发现促使我们将这个新结构域称为Ig“早期可变”（EV）集。值得注意的是，EV集与C1集结构域相连。据我们所知，C1集此前尚未在非脊椎动物中报道过。IgV和IgC1串联体以及它们组合形成功能性Ig样受体，是高等脊椎动物适应性免疫系统的一部分，可实现高度特异性的免疫反应。通过揭示祖先Ig结构域分子构型的重要线索，这些发现挑战并扩展了我们对免疫在当前格局中如何进化的理解。
