Child Health Institute of New Jersey, New Brunswick, NJ 08901, USA.
Department of Biology and Biotechnology "Charles Darwin" and Pasteur Institute - Cenci Bolognetti Foundation, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Structure. 2019 Jun 4;27(6):893-906.e9. doi: 10.1016/j.str.2019.03.004. Epub 2019 Apr 4.
In the developing brain, cell-surface proteins play crucial roles, but their protein-protein interaction network remains largely unknown. A proteomic screen identified 200 interactions, 89 of which were not previously published. Among these interactions, we find that the IgLONs, a family of five cell-surface neuronal proteins implicated in various human disorders, interact as homo- and heterodimers. We reveal their interaction patterns and report the dimeric crystal structures of Neurotrimin (NTRI), IgLON5, and the neuronal growth regulator 1 (NEGR1)/IgLON5 complex. We show that IgLONs maintain an extended conformation and that their dimerization occurs through the first Ig domain of each monomer and is Ca independent. Cell aggregation shows that NTRI and NEGR1 homo- and heterodimerize in trans. Taken together, we report 89 unpublished cell-surface ligand-receptor pairs and describe structural models of trans interactions of IgLONs, showing that their structures are compatible with a model of interaction across the synaptic cleft.
在发育中的大脑中，细胞表面蛋白起着至关重要的作用，但它们的蛋白质-蛋白质相互作用网络在很大程度上仍然未知。一项蛋白质组学筛选确定了 200 种相互作用，其中 89 种以前没有发表过。在这些相互作用中，我们发现 IgLONs 家族是五种与各种人类疾病有关的细胞表面神经元蛋白，它们可以作为同型和异型二聚体相互作用。我们揭示了它们的相互作用模式，并报告了 Neurotrimin（NTRI）、IgLON5 和神经元生长调节剂 1（NEGR1）/IgLON5 复合物的二聚体晶体结构。我们表明 IgLONs 保持伸展构象，并且它们的二聚化通过每个单体的第一个 Ig 结构域发生，并且不依赖于 Ca。细胞聚集表明 NTRI 和 NEGR1 同型和异型二聚体在顺式发生。总之，我们报告了 89 种未发表的细胞表面配体-受体对，并描述了 IgLONs 顺式相互作用的结构模型，表明它们的结构与跨突触间隙相互作用的模型兼容。
