Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects
Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects
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DOI：
10.1073/pnas.0610924104
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发表时间：
2007-04-17
影响因子：
11.1
通讯作者：
Lee, Bok-Luel
中科院分区：
文献类型：
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作者：
Park, Ji-Won;Kim, Chan-Hee;Lee, Bok-Luel
肽聚糖识别蛋白 (PGRP)-SA 对赖氨酸型肽聚糖的识别会引发 Toll 和酚氧化酶原途径的激活。在这里，我们揭示了赖氨酸型肽聚糖的可溶性片段，即具有短茎肽的长聚糖链，是果蝇 Toll 途径和甲虫黄粉虫中酚氧化酶原激活级联的有效激活剂。使用该肽聚糖片段，我们提供了生化证据，表明肽聚糖上 PGRP-SA 分子的聚集是激活酚氧化酶原级联反应所必需的。我们随后强调，溶菌酶介导的高度交联的赖氨酸型肽聚糖的部分消化显着增加了 PGRP-SA 的结合，可能是通过诱导 PGRP-SA 的聚集，然后招募革兰氏阴性细菌结合蛋白 1 同源物和含有低密度脂蛋白和补体控制的模块化丝氨酸蛋白酶 蛋白质结构域。通过使用溶菌酶抑制剂，在体内进一步证实了溶菌酶在酚氧化酶原激活级联中的关键作用。综上所述，我们提出了一个模型，其中溶菌酶呈现赖氨酸型肽聚糖的加工形式，用于 PGRP-SA 的聚集，招募革兰氏阴性细菌结合蛋白 1 和模块化丝氨酸蛋白酶，从而导致 Toll 和酚氧化酶原途径的激活。
Recognition of lysine-type peptidoglycan by peptidoglycan recognition protein (PGRP)-SA provokes the activation of the Toll and prophenoloxidase pathways. Here we reveal that a soluble fragment of lysine-type peptidoglycan, a long glycan chain with short stem peptides, is a potent activator of the Drosophila Toll pathway and the prophenoloxidase activation cascade in the beetle Tenebrio molitor. Using this peptidoglycan fragment, we present biochemical evidence that clustering of PGRP-SA molecules on the peptidoglycan is required for the activation of the prophenoloxidase cascade. We subsequently highlight that the lysozymemediated partial digestion of highly cross-linked lysine-type peptidoglycan dramatically increases the binding of PGRP-SA, presumably by inducing clustering of PGRP-SA, which then recruits the Gram-negative bacteria-binding protein 1 homologue and a modular serine protease containing low-density lipoprotein and complement control protein domains. The crucial role of lysozyme in the prophenoloxidase activation cascade is further confirmed in vivo by using a lysozyme inhibitor. Taken together, we propose a model whereby lysozyme presents a processed form of lysine-type peptidoglycan for clustering of PGRP-SA that recruits Gram-negative bacteria-binding protein 1 and the modular serine protease, which leads to the activation of both the Toll and prophenoloxidase pathways.