Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA.
J Biol Chem. 2023 Jun;299(6):104758. doi: 10.1016/j.jbc.2023.104758. Epub 2023 Apr 26.
Microbial recognition is a key step in regulating the immune signaling pathways of multicellular organisms. Peptidoglycan, a component of the bacterial cell wall, exhibits immune stimulating activity in both plants and animals. Lysin motif domain (LysMD) family proteins are ancient peptidoglycan receptors that function in bacteriophage and plants. This report focuses on defining the role of LysMD-containing proteins in animals. Here, we characterize a novel transmembrane LysMD family protein. Loss-of-function mutations at the lysMD3/4 locus in Drosophila are associated with systemic innate immune activation following challenge, so we refer to this gene as immune active (ima). We show that Ima selectively binds peptidoglycan, is enriched in cell membranes, and is necessary to regulate terminal innate immune effectors through an NF-kB-dependent pathway. Hence, Ima fulfills the key criteria of a peptidoglycan pattern recognition receptor. The human Ima ortholog, hLysMD3, exhibits similar biochemical properties. Together, these findings establish LysMD3/4 as the founding member of a novel family of animal peptidoglycan recognition proteins.
微生物识别是调节多细胞生物免疫信号通路的关键步骤。肽聚糖是细菌细胞壁的一个组成部分，在植物和动物中都具有免疫刺激活性。溶菌酶结构域 (LysMD) 家族蛋白是古老的肽聚糖受体，在噬菌体和植物中发挥作用。本报告重点介绍了含 LysMD 蛋白在动物中的作用。在这里，我们描述了一种新型跨膜 LysMD 家族蛋白。果蝇中 lysMD3/4 基因座的功能丧失突变与受到挑战后全身固有免疫激活有关，因此我们将该基因称为免疫激活（ima）。我们表明，Ima 选择性地结合肽聚糖，在细胞膜中富集，并通过 NF-κB 依赖性途径调节末端固有免疫效应器。因此，Ima 满足肽聚糖模式识别受体的关键标准。人类 Ima 同源物 hLysMD3 表现出相似的生化特性。综上所述，这些发现确立了 LysMD3/4 作为新型动物肽聚糖识别蛋白家族的创始成员。
