The discovery that sponges (Porifera) can fully regenerate from aggregates of dissociated cells launched them as one of the earliest experimental models to study the evolution of cell adhesion and allorecognition in animals. This process depends on an extracellular glycoprotein complex called the Aggregation Factor (AF), which is composed of proteins thought to be unique to sponges. We used quantitative proteomics to identify additional AF components and interacting proteins in the classical model, Clathria prolifera , and compared them to proteins involved in cell interactions in Bilateria. Our results confirm MAFp3/p4 proteins as the primary components of the AF but implicate related proteins with calx-beta and wreath domains as additional components. Using AlphaFold, we unveiled close structural similarities of AF components to protein domains in other animals, previously masked by the mutational decay of sequence similarity. The wreath domain, believed to be unique to the AF, was predicted to contain a central beta-sandwich of the same organization as the vWFD domain (also found in extracellular, gel-forming glycoproteins in other animals). Additionally, many copurified proteins share a conserved C-terminus, containing divergent immunoglobulin (Ig) and Fn3 domains predicted to serve as an AF–interaction interface. One of these proteins, MAF-associated protein 1, resembles Ig superfamily cell adhesion molecules and we hypothesize that it may function to link the AF to the surface of cells. Our results highlight the existence of an ancient toolkit of conserved protein domains regulating cell–cell and cell–extracellular matrix protein interactions in all animals, and likely reflect a common origin of cell adhesion and allorecognition.

中文翻译：

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海绵聚集因子的蛋白质组学分析表明，动物体内的同种异体识别和粘附是一种古老的工具包


海绵 （Porifera） 可以从解离细胞的聚集体中完全再生的发现使它们成为研究动物细胞粘附和同种异体识别进化的最早实验模型之一。这个过程取决于一种称为聚集因子 （AF） 的细胞外糖蛋白复合物，它由被认为是海绵独有的蛋白质组成。我们使用定量蛋白质组学来鉴定经典模型 Clathria prolifera 中的其他 AF 成分和相互作用蛋白，并将它们与 Bilateria 中参与细胞相互作用的蛋白质进行比较。我们的结果证实 MAFp3/p4 蛋白是 AF 的主要成分，但暗示与 calx-beta 和 wreath 结构域相关的蛋白质是额外的成分。使用 AlphaFold，我们揭示了 AF 成分与其他动物蛋白质结构域的紧密结构相似性，这些结构域以前被序列相似性的突变衰减所掩盖。据信是 AF 独有的花环结构域，预计包含与 vWFD 结构域具有相同组织的中央 β 夹心（也存在于其他动物的细胞外凝胶形成糖蛋白中）。此外，许多共纯化的蛋白质共享一个保守的 C 端，包含不同的免疫球蛋白 （Ig） 和 Fn3 结构域，预计用作 AF 相互作用界面。其中一种蛋白质 MAF 相关蛋白 1 类似于 Ig 超家族细胞粘附分子，我们假设它可能起到将 AF 连接到细胞表面的作用。我们的结果强调了一种古老的保守蛋白质结构域工具包的存在，该工具包调节所有动物中的细胞-细胞和细胞-细胞外基质蛋白相互作用，并且可能反映了细胞粘附和同种异体识别的共同起源。