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果蝇肽聚糖识别蛋白 LF 与肽聚糖识别蛋白 LC 相互作用，下调 Imd 途径。

The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway.

机构信息

Centre de Biophysique Moléculaire, UPR 4301 CNRS, Rue Charles Sadron, Orléans 2 45071, France.

出版信息

EMBO Rep. 2011 Apr;12(4):327-33. doi: 10.1038/embor.2011.19. Epub 2011 Mar 4.

DOI:10.1038/embor.2011.19
PMID:21372849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3077246/
Abstract

The peptidoglycan (PGN)-recognition protein LF (PGRP-LF) is a specific negative regulator of the immune deficiency (Imd) pathway in Drosophila. We determine the crystal structure of the two PGRP domains constituting the ectodomain of PGRP-LF at 1.72 and 1.94 Å resolution. The structures show that the LFz and LFw domains do not have a PGN-docking groove that is found in other PGRP domains, and they cannot directly interact with PGN, as confirmed by biochemical-binding assays. By using surface plasmon resonance analysis, we show that the PGRP-LF ectodomain interacts with the PGRP-LCx ectodomain in the absence and presence of tracheal cytotoxin. Our results suggest a mechanism for downregulation of the Imd pathway on the basis of the competition between PRGP-LCa and PGRP-LF to bind to PGRP-LCx.

摘要

肽聚糖（PGN）识别蛋白 LF（PGRP-LF）是果蝇免疫缺陷（Imd）途径的特异性负调节剂。我们确定了由 PGRP-LF 的胞外结构域组成的两个 PGRP 结构域的晶体结构，分辨率分别为 1.72 和 1.94 Å。这些结构表明，LFz 和 LFw 结构域没有其他 PGRP 结构域中发现的 PGN 结合槽，并且它们不能直接与 PGN 相互作用，这一点通过生化结合测定得到了证实。通过表面等离子体共振分析，我们表明在存在和不存在气管细胞毒素的情况下，PGRP-LF 胞外结构域与 PGRP-LCx 胞外结构域相互作用。我们的结果表明，基于 PRGP-LCa 和 PGRP-LF 与 PGRP-LCx 结合的竞争，存在一种下调 Imd 途径的机制。

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本文引用的文献

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PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling.PIMS通过负向调节果蝇先天免疫信号传导来调节免疫耐受。
Cell Host Microbe. 2008 Aug 14;4(2):147-58. doi: 10.1016/j.chom.2008.07.004.
2
The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation.果蝇肽聚糖识别蛋白PGRP-LF可阻断PGRP-LC及IMD/JNK信号通路的激活。
Cell Host Microbe. 2008 May 15;3(5):293-303. doi: 10.1016/j.chom.2008.04.002.
3
Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan.果蝇PGRP-SD的晶体结构表明其与DAP型肽聚糖结合，但不与赖氨酸型肽聚糖结合。
Mol Immunol. 2008 May;45(9):2521-30. doi: 10.1016/j.molimm.2008.01.015. Epub 2008 Mar 4.
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Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila.果蝇中同源异型框基因尾端维持的先天免疫稳态与共生肠道互利共生关系
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Peptidoglycan recognition protein LF: a negative regulator of Drosophila immunity.肽聚糖识别蛋白LF：果蝇免疫的负调节因子。
Insect Biochem Mol Biol. 2007 Dec;37(12):1309-16. doi: 10.1016/j.ibmb.2007.08.003. Epub 2007 Aug 21.
6
The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections.果蝇的系统性免疫反应：细菌和真菌感染期间的感知与信号传导
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Capturing protein-protein complexes at equilibrium: the holdup comparative chromatographic retention assay.在平衡状态下捕获蛋白质-蛋白质复合物：滞留比较色谱保留测定法。
Protein Expr Purif. 2006 Nov;50(1):89-101. doi: 10.1016/j.pep.2006.06.010. Epub 2006 Jun 27.
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The Drosophila amidase PGRP-LB modulates the immune response to bacterial infection.果蝇酰胺酶PGRP-LB调节对细菌感染的免疫反应。
Immunity. 2006 Apr;24(4):463-73. doi: 10.1016/j.immuni.2006.02.012.
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Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor.与异源二聚体模式识别受体复合的气管细胞毒素结构
Science. 2006 Mar 24;311(5768):1761-4. doi: 10.1126/science.1123056.
10
Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2.肽聚糖识别蛋白SC1和SC2对果蝇免疫反应的下调作用。
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