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纯化的单体配体-MD-2复合物揭示了革兰氏阴性细菌内毒素激活和拮抗TLR4的分子和结构要求。

Purified monomeric ligand.MD-2 complexes reveal molecular and structural requirements for activation and antagonism of TLR4 by Gram-negative bacterial endotoxins.

作者信息

Gioannini Theresa L, Teghanemt Athmane, Zhang DeSheng, Esparza Gregory, Yu Liping, Weiss Jerrold

机构信息

The Inflammation Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 2501 Crosspark Rd, Coralville, IA, 52241, USA.

出版信息

Immunol Res. 2014 Aug;59(1-3):3-11. doi: 10.1007/s12026-014-8543-y.

DOI:10.1007/s12026-014-8543-y
PMID:24895101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4125468/
Abstract

A major focus of work in our laboratory concerns the molecular mechanisms and structural bases of Gram-negative bacterial endotoxin recognition by host (e.g., human) endotoxin-recognition proteins that mediate and/or regulate activation of Toll-like receptor (TLR) 4. Here, we review studies of wild-type and variant monomeric endotoxin.MD-2 complexes first produced and characterized in our laboratories. These purified complexes have provided unique experimental reagents, revealing both quantitative and qualitative determinants of TLR4 activation and antagonism. This review is dedicated to the memory of Dr. Theresa L. Gioannini (1949-2014) who played a central role in many of the studies and discoveries that are reviewed.

摘要

我们实验室的主要工作重点是宿主(如人类)内毒素识别蛋白识别革兰氏阴性菌内毒素的分子机制和结构基础,这些蛋白介导和/或调节Toll样受体(TLR)4的激活。在此,我们综述了在我们实验室首次产生并表征的野生型和变体单体内毒素-MD-2复合物的研究。这些纯化的复合物提供了独特的实验试剂,揭示了TLR4激活和拮抗作用的定量和定性决定因素。这篇综述是为了纪念特蕾莎·L·乔阿尼尼博士(1949-2014),她在许多被综述的研究和发现中发挥了核心作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/7a466e3fba13/nihms601771f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/791f3d442a87/nihms601771f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/f36ec35f645d/nihms601771f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/2136bbaf3ff1/nihms601771f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/7a466e3fba13/nihms601771f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/8360251f658f/nihms601771f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/6c616c6d0a9d/nihms601771f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/fe767ff2d034/nihms601771f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/791f3d442a87/nihms601771f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/f36ec35f645d/nihms601771f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/2136bbaf3ff1/nihms601771f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b5/4125468/7a466e3fba13/nihms601771f7.jpg

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本文引用的文献

1
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2
Tetraacylated lipid A and paclitaxel-selective activation of TLR4/MD-2 conferred through hydrophobic interactions.四酰化脂质 A 通过疏水相互作用选择性激活 TLR4/MD-2 和紫杉醇。
J Immunol. 2014 Feb 15;192(4):1887-95. doi: 10.4049/jimmunol.1302119. Epub 2014 Jan 13.
3
Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis.
Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery.
酰氧基酰基水解酶对细菌脂多糖的生化转化可减轻宿主损伤,促进恢复。
J Biol Chem. 2020 Dec 18;295(51):17842-17851. doi: 10.1074/jbc.REV120.015254.
4
Escherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy.大肠杆菌黏附部分 FimH 可作为癌症免疫治疗的佐剂。
Nat Commun. 2020 Mar 4;11(1):1187. doi: 10.1038/s41467-020-15030-4.
5
Memory-Like Inflammatory Responses of Microglia to Rising Doses of LPS: Key Role of PI3Kγ.小胶质细胞对 LPS 递增剂量的类记忆炎症反应:PI3Kγ 的关键作用。
Front Immunol. 2019 Nov 8;10:2492. doi: 10.3389/fimmu.2019.02492. eCollection 2019.
6
Household endotoxin reduction in the Louisa Environmental Intervention Project for rural childhood asthma.农村儿童哮喘路易莎环境干预项目中的家庭内毒素减少。
Indoor Air. 2020 Jan;30(1):88-97. doi: 10.1111/ina.12610. Epub 2019 Nov 22.
7
5-Aza-2'-deoxycytidine enhances lipopolysaccharide-induced inflammatory cytokine expression in human dental pulp cells by regulating TRAF6 methylation.5-Aza-2'-脱氧胞苷通过调节 TRAF6 甲基化增强脂多糖诱导的人牙髓细胞炎症细胞因子表达。
Bioengineered. 2019 Dec;10(1):197-206. doi: 10.1080/21655979.2019.1621135.
8
Detecting lipopolysaccharide in the cytosol of mammalian cells: Lessons from MD-2/TLR4.检测哺乳动物细胞胞质中的脂多糖:MD-2/TLR4 的启示。
J Leukoc Biol. 2019 Jul;106(1):127-132. doi: 10.1002/JLB.3MIR1118-434R. Epub 2019 Jan 29.
9
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4
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5
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9
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10
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J Immunol. 2010 Apr 15;184(8):4362-7. doi: 10.4049/jimmunol.0903142. Epub 2010 Mar 8.