肽聚糖识别蛋白(PGRPs或PGLYRPs)是先天免疫分子，包含一个保守的肽聚糖结合2型酰胺酶结构域，与噬菌体和细菌2型酰胺酶同源(Kang D et al. 1998;刘灿等2001;Royet J and Dziarski R 2007;Royet J et al. 2011;Dziarski R et al. 2016)。哺乳动物有四个pgrp家族(PGLYRP1, 2,3和4)，它们以细胞类型或组织特异性的方式不同地表达。人PGLYRP3和PGLYRP4(也称为PGRP- Ialpha和PGRP- ibeta)在角质形成细胞和上皮细胞中表达，并在皮肤、眼睛、唾流腺、咽喉、舌头、食道、胃和肠中发现(Liu C et al. 2001;Lu X et al. 2006)。与PGLYRP1一样，PGLYRP3和PGLYRP4作为二硫键连接的同源二聚体分泌(Guan R et al. 2004, 2005;Lu X et al. 2006)。 However, PGLYRP3 and PGLYRP4 preferentially form heterodimers when coexpressed in the same cells (Lu X et al. 2006). PGLYRP3, PGLYRP4, and PGLYRP3:PGLYRP4 have Zn(2+)‑dependent bactericidal activity against both Gram‑positive and Gram‑negative bacteria at the physiological Zn(2+) concentrations found in serum, sweat, saliva, and other body fluids (Lu X et al. 2006; Wang M et al. 2007). PGLYRP3 and PGLYRP4 are also active against Chlamydia trachomatis (Bobrovsky P et al. 2016). Killing of both Gram-positive and Gram-negative bacteria by PGLYRP3 and PGLYRP4 is synergistically enhanced by antimicrobial peptides (phospholipase A2, alpha- and beta-defensins, and bactericidal permeability-increasing protein (BPI)) (Wang M et al. 2007). The bactericidal activity of PGRPs requires their N‑glycosylation, as deglycosylation with N‑glycosidase abolished their bactericidal activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli (Lu X et al. 2006; Wang M et al. 2007).
pgrp被认为是通过与细胞壁肽聚糖相互作用和在细菌中诱导致死应激反应而杀死细菌的，而不是通过水解肽聚糖或通过其他抗菌肽渗透细菌膜(Lu X et al. 2006;王敏等2007;Cho S et al. 2007;Kashyap DR et al. 2011, 2014)。在包括枯草芽孢杆菌在内的革兰氏阳性细菌中，发现PGLYRP1、3和4在细胞分裂过程中在子细胞分离位点进入细菌细胞壁，并在细胞膜附近与细胞壁肽聚糖结合(Kashyap DR et al. 2011)。PGLYRP3与肽聚糖的结合诱导了PGLYRP3的结构变化，从而将肽聚糖锁在蛋白的绑定槽中(Guan R等，2006)。然而，这种结合并没有抑制肽聚糖合成中的细胞外转糖基化或转肽化步骤(Kashyap DR et al. 2011)，这是众所周知的杀菌抗生素的靶点。相反，PGRP蛋白与肽聚糖的这种相互作用激活了枯草芽孢杆菌包膜应激反应双组分系统csssr - CssS，该系统检测并处理从细菌细胞输出的错误折叠蛋白。这种激活导致细菌膜去极化，停止细胞内肽聚糖、蛋白质、RNA和DNA的合成和有毒羟基自由基的产生，这是导致细菌死亡的原因(Kashyap DR et al. 2011)。在革兰氏阴性菌(大肠杆菌)中，发现PGRPs结合细菌外膜，激活功能同源的CpxA - CpxR双组分系统(Kashyap DR et al. 2011)。 Genome expression arrays, qRT‑PCR, and biochemical tests showed that PGLYRP3 & 4 kill both E. coli and B. subtilis by inducing oxidative, thiol, and metal stress (Kashyap DR et al. 2014).
