PGLYRP1

肽聚糖识别蛋白1（Peptidoglycan Recognition Protein 1），也被称为 TAG7、PGRP-S，是在人类PGLYRP1基因编码的蛋白。^[5][6][7]

PGLYRP1
已知的结构 PDB 直系同源搜索: PDBe RCSB PDBID列表 1YCK
识别号
别名	PGLYRP1；, PGLYRP, PGRP, PGRP-S, PGRPS, TAG7, TNFSF3L, peptidoglycan recognition protein 1
外部ID	OMIM：604963 MGI：1345092 HomoloGene：74539 GeneCards：PGLYRP1
基因位置（人类） 染色体 19号染色体[1] 基因座 19q13.32 起始 46,019,153 bp[1] 终止 46,023,053 bp[1]
基因位置（小鼠） 染色体 小鼠7号染色体[2] 基因座 7|7 A3 起始 18,605,256 bp[2] 终止 18,624,384 bp[2]
RNA表达模式
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基因本体 分子功能 • 锌离子结合 • peptidoglycan immune receptor activity • N-acetylmuramoyl-L-alanine amidase activity • peptidoglycan binding 细胞组分 • 外排体 • 细胞外区域 • specific granule lumen • phagocytic vesicle lumen • tertiary granule lumen • 细胞外空间 生物学过程 • peptidoglycan catabolic process • negative regulation of natural killer cell differentiation involved in immune response • negative regulation of interferon-gamma production • 先天免疫系统 • negative regulation of inflammatory response • defense response to bacterium • 免疫反应 • detection of bacterium • immune system process • defense response to Gram-positive bacterium • pattern recognition receptor signaling pathway • antimicrobial humoral response • neutrophil degranulation • positive regulation of cytolysis in other organism • antimicrobial humoral immune response mediated by antimicrobial peptide • response to bacterium • killing of cells of other organism Sources:Amigo / QuickGO
直系同源
物种	人类	小鼠
Entrez	8993	21946
Ensembl	ENSG00000008438	ENSMUSG00000030413
UniProt	O75594	O88593
mRNA​序列	NM_005091	NM_009402
蛋白序列	NP_005082	NP_033428
基因位置​（UCSC）	Chr 19: 46.02 – 46.02 Mb	Chr 7: 18.61 – 18.62 Mb
PubMed​查找	[3]	[4]
维基数据
查看/编辑人类 查看/编辑小鼠

肽聚糖识别蛋白（Peptidoglycan Recognition Proteins, PGRPs）是近几年来，在昆虫和哺乳动物体内所发现的一种先天性免疫激活蛋白。哺乳动物具有四种PGRPs，分别命名为PGRP-S、PGRP-L、PGRP-Iα以及PGRP-Iβ（也称为PGLYRP-1、PGLYRP-2、PGLYRP-3与PGLYRP-4）。^[8]

其中，PGRP-S为哺乳动物PGRP中最早克隆得到的。在过去的试验发现PGRP-S会活化生物体的淋巴免疫细胞而诱发体内生成干扰素（IFN-γ）、肿瘤坏死因子（TNF-α），^[9]而展现出抗病毒的效果，且受到PGRP-S活化的淋巴免疫细胞并不会对正常的健康细胞产生危害。^[10]

组织分布与分泌

该PGLYRP-1基因会高度表现在骨髓、循环型多形核白细胞（PMLs），以及角膜上皮细胞。主要在颗粒多型核白血球（PML）可以发现PGLYRP1蛋白。

结构

如同大多数肽聚糖识别蛋白，PGLYRP-1有一个羧基端第2型酰胺域（也称为PGRP域）并包括三个α-螺旋，五个β股，螺旋，并具有能形成三个双硫键的三对保守半胱氨酸。^[11] PGLYRP1会形成二聚体，以表现出抗微生物活性，并且可以与热休克蛋白70形成复合体，而表现出其毒性。

功能

PGLYRP-1蛋白在先天免疫反应中扮演著极为重要的脚色。 此蛋白针对革兰氏阳性菌，例如金黄色葡萄球菌、表皮葡萄球菌以及李斯特菌，且通常具有促炎的影响，会诱发组织中肿瘤坏死因子-α（TNF-a）和干扰素伽玛（IFN-γ）的生成，对于猪PRRS病毒、流感病毒以及肠病毒在研究中也能产生出抑制的效果。^{[10][12][13][14][15]}

在过去的研究中，我们也知道PGLYRP-1能与热休克蛋白70形成具有细胞毒性的复合体，这表示了它也许能作为抗癌症的脚色。^[16] 身为一个具有抗菌属性的识别病原蛋白，PGLYRP-1也许在维持肠道中微生物菌丛中扮演著重要脚色。

机制

作为抗微生物剂，PGLYRP-1结合到其目标细胞，并不会像防御素和其他抗菌肽一样，穿透细菌细胞壁。 相反地，PGLYRP-1的结合激活了细菌的压抑反应，而导致细菌关闭转录和转译作用，以及诱导氧化反应。作为一个细胞毒性剂，PGLYRP1-热休克蛋白70复合体

可能的病理学作用

在人体上，PGLYRP-1基因的单核苷酸多态性与溃疡性结肠炎的发生有关。^[17]

在小鼠，缺乏PGLYRP1会增加感染传染性疾病的机率，但也减少了自体免疫性疾病的侵扰。当感染绿脓杆菌时，缺乏 PGLYRP1会增加角膜感染的风险性，减少角膜创伤的愈合能力，并且增加了角膜刮伤。^[18] 但PGLYRP1缺陷的小鼠同时也减缓了过敏性皮肤炎和接触性皮肤炎的严重性，且对于哮喘的发生也有所影响。

参考文献

1. GRCh38: Ensembl release 89: ENSG00000008438 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030413 - Ensembl, May 2017
3. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc Natl Acad Sci U S A. Sep 1998, 95 (17): 10078–82. PMC 21464 . PMID 9707603. doi:10.1073/pnas.95.17.10078.
6. [Expression analysis of proteins encoded by genes of the tag7/tagL (PGRP-S,L) family in human peripheral blood cells]. Genetika. Apr 2003, 39 (2): 244–9. PMID 12669421.
7. Entrez Gene: PGLYRP1 peptidoglycan recognition protein 1.
8. 郭, 睿; 王, 银. 哺乳动物肽聚糖识别蛋白抗菌作用及其机制的研究进展. 吉林农业大学学报. 2013, 35 (02): 236–240 [2019-01-15]. ISSN 1000-5684. doi:10.13327/j.jjlau.2013.02.023. （原始内容存档于2019-01-15）.
9. Osanai, Arihiro; Sashinami, Hiroshi; Asano, Krisana; Li, Sheng-Jun; Hu, Dong-Liang; Nakane, Akio. Mouse Peptidoglycan Recognition Protein PGLYRP-1 Plays a Role in the Host Innate Immune Response againstListeria monocytogenesInfection. Infection and Immunity. 2010-12-06, 79 (2): 858–866. ISSN 0019-9567. doi:10.1128/iai.00466-10.
10. Sharapova, Tatiana N.; Ivanova, Olga K.; Prasolov, Vladimir S.; Romanova, Elena A.; Sashchenko, Lidia P.; Yashin, Denis V. Innate immunity protein Tag7 (PGRP-S) activates lymphocytes capable of Fasl-Fas-dependent contact killing of virus-infected cells. IUBMB Life. 2017-10-30, 69 (12): 971–977. ISSN 1521-6543. doi:10.1002/iub.1688.
11. Crystal structure of human peptidoglycan recognition protein I alpha bound to a muramyl pentapeptide from Gram-positive bacteria. Protein Sci. 2006, 15 (5): 1199–206. PMC 2242522 . PMID 16641493. doi:10.1110/ps.062077606.
12. López-Fuertes, L; Campos, E; Doménech, N; Ezquerra, A; Castro, J.M; Domı́nguez, J; Alonso, F. Porcine reproductive and respiratory syndrome (PRRS) virus down-modulates TNF-α production in infected macrophages. Virus Research. 2000-08, 69 (1): 41–46. ISSN 0168-1702. doi:10.1016/s0168-1702(00)00172-6.
13. Bautista, E. M.; Molitor, T. W. IFNγ inhibits porcine reproductive and respiratory syndrome virus replication in macrophages. Archives of Virology. 1999-06, 144 (6): 1191–1200. ISSN 0304-8608. doi:10.1007/s007050050578.
14. Weiss, Ido D.; Wald, Ori; Wald, Hanna; Beider, Katia; Abraham, Michal; Galun, Eithan; Nagler, Arnon; Peled, Amnon. IFN-γ Treatment at Early Stages of Influenza Virus Infection Protects Mice from Death in a NK Cell-Dependent Manner. Journal of Interferon & Cytokine Research. 2010-06, 30 (6): 439–449. ISSN 1079-9907. doi:10.1089/jir.2009.0084.
15. Hoshino, Akinori; Takenaka, Hiroshi; Mizukoshi, Osamu; Imanishi, Jiro; Kishida, Tsunataro; Tovey, Michael G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.
16. Peptidoglycan recognition protein tag7 forms a cytotoxic complex with heat shock protein 70 in solution and in lymphocytes. J. Biol. Chem. 2004, 279 (3): 2117–24. PMID 14585845. doi:10.1074/jbc.M307513200.
17. Genetic Association of Peptidoglycan Recognition Protein Variants with Inflammatory Bowel Disease. PLoS ONE. 2013, 8 (6): e67393. PMC 3686734 . PMID 23840689. doi:10.1371/journal.pone.0067393.
18. A novel antimicrobial peptidoglycan recognition protein in the cornea. Invest. Ophthalmol. Vis. Sci. 2009, 50 (9): 4185–91. PMC 3052780 . PMID 19387073. doi:10.1167/iovs.08-3040.

相关阅读

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