Wang Lihui, Weber Alexander N R, Atilano Magda L, Filipe Sergio R, Gay Nicholas J, Ligoxygakis Petros
Genetics Unit, Department of Biochemistry, University of Oxford, Oxford, UK.
EMBO J. 2006 Oct 18;25(20):5005-14. doi: 10.1038/sj.emboj.7601363. Epub 2006 Oct 5.
Genetic evidence indicates that Drosophila defense against Gram-positive bacteria is mediated by two putative pattern recognition receptors acting upstream of Toll, namely Gram-negative binding protein 1 (GNBP1) and peptidoglycan recognition protein SA (PGRP-SA). Until now however, the molecular recognition proceedings for sensing of Gram-positive pathogens were not known. In the present, we report the physical interaction between GNBP1 and PGRP-SA using recombinant proteins. GNBP1 was able to hydrolyze Gram-positive peptidoglycan (PG), while PGRP-SA bound highly purified PG fragments (muropeptides). Interaction between these proteins was enhanced in the presence of PG or muropeptides. PGRP-SA binding depended on the polymerization status of the muropeptides, pointing to constraints in the number of PGRP-SA molecules bound for signaling initiation. We propose a model whereby GNBP1 presents a processed form of PG for sensing by PGRP-SA and that a tripartite interaction between these proteins and PG is essential for downstream signaling.
遗传学证据表明，果蝇对革兰氏阳性菌的防御是由两种假定的模式识别受体介导的，它们作用于Toll上游，即革兰氏阴性结合蛋白1（GNBP1）和肽聚糖识别蛋白SA（PGRP-SA）。然而，迄今为止，感知革兰氏阳性病原体的分子识别过程尚不清楚。在本研究中，我们利用重组蛋白报道了GNBP1和PGRP-SA之间的物理相互作用。GNBP1能够水解革兰氏阳性肽聚糖（PG），而PGRP-SA结合高度纯化的PG片段（胞壁肽）。在PG或胞壁肽存在的情况下，这些蛋白之间的相互作用增强。PGRP-SA的结合取决于胞壁肽的聚合状态，这表明信号启动时结合的PGRP-SA分子数量存在限制。我们提出了一个模型，即GNBP1呈递一种经过加工的PG形式以供PGRP-SA感知，并且这些蛋白与PG之间的三方相互作用对于下游信号传导至关重要。
