Chamaillard Mathias, Hashimoto Masahito, Horie Yasuo, Masumoto Junya, Qiu Su, Saab Lisa, Ogura Yasunori, Kawasaki Akiko, Fukase Koichi, Kusumoto Shoichi, Valvano Miguel A, Foster Simon J, Mak Tak W, Nuñez Gabriel, Inohara Naohiro
Department of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nat Immunol. 2003 Jul;4(7):702-7. doi: 10.1038/ni945. Epub 2003 Jun 6.
Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan.
核苷酸结合寡聚化结构域蛋白1（NOD1）属于一个家族，该家族在脊椎动物和植物中包含多个具有NOD和富含亮氨酸重复序列的成员。有人提出NOD1在先天免疫反应中起作用，但其中涉及的机制尚不清楚。在此我们报告，NOD1介导对主要来源于革兰氏阴性菌的肽聚糖的识别。使用高度纯化的合成化合物进行的生化和功能分析表明，NOD1识别的核心结构是一种二肽，γ-D-谷氨酰-间二氨基庚二酸（iE-DAP）。缺乏NOD1的小鼠巨噬细胞对合成的iE-DAP无反应分泌细胞因子，也不能引发脂多糖反应。因此，NOD1通过检测含iE-DAP的肽聚糖介导对细菌的选择性识别。
