The N-terminal Domain of Drosophila Gram-negative Binding Protein 3 (GNBP3) Defines a Novel Family of Fungal Pattern Recognition Receptors
The N-terminal Domain of Drosophila Gram-negative Binding Protein 3 (GNBP3) Defines a Novel Family of Fungal Pattern Recognition Receptors
复制标题
DOI：
10.1074/jbc.m109.034587
复制
发表时间：
2009-10-16
影响因子：
4.8
通讯作者：
Roussel, Alain
中科院分区：
文献类型：
--
作者：
Mishima, Yumiko;Quintin, Jessica;Roussel, Alain
革兰氏阴性结合蛋白3(GNBP3)是果蝇血淋巴中的一种模式识别受体，负责感知真菌感染和触发Toll通路的激活。在这里，我们报告了GNBP3的N-末端结构域在确定真菌细胞壁中的长链β-1，3-葡聚糖链为主要配体后与真菌结合。有趣的是，这个结构域不能与短寡糖发生强烈的相互作用。GNBP3-Enter的晶体结构显示了一个类免疫球蛋白的折叠，其中葡聚糖结合部位被一个在几个昆虫目中发现的葡聚糖结合蛋白中高度保守的环所掩盖。基于结构的突变实验揭示了这种闭塞环在区分短和长多糖方面的重要作用。封闭环的位移是结合所必需的，可以解释与长链结构多糖相互作用的特异性。这代表了一种识别β-葡聚糖的新机制。
Gram-negative binding protein 3 (GNBP3), a pattern recognition receptor that circulates in the hemolymph of Drosophila, is responsible for sensing fungal infection and triggering Toll pathway activation. Here, we report that GNBP3 N-terminal domain binds to fungi upon identifying long chains of beta-1,3-glucans in the fungal cell wall as a major ligand. Interestingly, this domain fails to interact strongly with short oligosaccharides. The crystal structure of GNBP3-Nter reveals an immunoglobulin-like fold in which the glucan binding site is masked by a loop that is highly conserved among glucan-binding proteins identified in several insect orders. Structure-based mutagenesis experiments reveal an essential role for this occluding loop in discriminating between short and long polysaccharides. The displacement of the occluding loop is necessary for binding and could explain the specificity of the interaction with long chain structured polysaccharides. This represents a novel mechanism for beta-glucan recognition.