Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2

Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2
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DOI:
10.1074/jbc.m307198200
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发表时间:
2003-10-24
影响因子:
4.8
通讯作者:
Mengin-Lecreulx, D
Mengin-Lecreulx, D
中科院分区:
生物学2区
文献类型:
--
作者:
Girardin, SE;Travassos, LH;Mengin-Lecreulx, D

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Nod 1和Nod 2是涉及病原体相关分子模式的细胞内检测的哺乳动物蛋白质。最近,天然存在的肽聚糖(PG)片段被鉴定为Nod 1和Nod 2所感知的微生物基序。而Nod 2检测GlcNAc-MurNAc二肽(GM-Di),Nod 1感测主要在革兰氏阴性细菌PG中发现的独特的含有二氨基庚二酸的GlcNAc-MurNAc三肽尿肽(GM-Tri(DAP))。由于Nod 1和Nod 2检测相似但不同的尿肽,我们进一步分析了Nod 1和Nod 2对PG片段的分子传感特异性。使用广泛的天然或修饰的胞壁肽,我们在这里显示,Nod 1和Nod 2已经进化出不同的策略,以实现PG传感。通过定义Nod 1和Nod 2传感的PG结构要求,本研究揭示了PG加工和修饰,无论是宿主还是细菌酶,可能会影响先天免疫反应。
Nod1 and Nod2 are mammalian proteins implicated in the intracellular detection of pathogen-associated molecular patterns. Recently, naturally occurring peptidoglycan ( PG) fragments were identified as the microbial motifs sensed by Nod1 and Nod2. Whereas Nod2 detects GlcNAc-MurNAc dipeptide (GM-Di), Nod1 senses a unique diaminopimelate-containing GlcNAc-MurNAc tripeptide muropeptide (GM-Tri(DAP)) found mostly in Gram-negative bacterial PGs. Because Nod1 and Nod2 detect similar yet distinct muropeptides, we further analyzed the molecular sensing specificity of Nod1 and Nod2 toward PG fragments. Using a wide array of natural or modified muramyl peptides, we show here that Nod1 and Nod2 have evolved divergent strategies to achieve PG sensing. By defining the PG structural requirements for Nod1 and Nod2 sensing, this study reveals how PG processing and modifications, either by host or bacterial enzymes, may affect innate immune responses.