共查询到20条相似文献，搜索用时 15 毫秒
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为进一步研究肽聚糖识别蛋白(peptidoglycan recognition proteins,PGRPs)在先天性免疫应答中的生物学功能,在前期克隆黄颡鱼长型肽聚糖识别蛋白(pfPGRP-L)c DNA全长的基础上,根据pfPGRP-L基因中高亲水性区域序列设计特异性引物扩增出编码序列,将该基因片段克隆到p GEX-4T-1质粒,构建重组表达载体。SDS-PAGE电泳检测该目的蛋白大小约为51 ku,与理论值大小符合,回收蛋白并纯化,与弗氏佐剂等量混合后注射新西兰大白兔制备多克隆抗体,用ELISA和Western blotting分别检测该抗体,结果显示:抗体效价可达1∶256 000,且有特异性条带,表明pfPGRP-L的多克隆抗体制备成功。此外,Western blotting检测黄颡鱼不同组织pfPGRP-L蛋白的表达,发现在鳃、胸腺、肝脏、肾脏、头肾、脾脏、血液和肠道等不同组织中都有目的条带,而在脾脏和肠道中表达更强。为pfPGRP-L的抗菌作用和功能研究奠定基础。 相似文献
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Koropatnick TA Engle JT Apicella MA Stabb EV Goldman WE McFall-Ngai MJ 《Science (New York, N.Y.)》2004,306(5699):1186-1188
Tracheal cytotoxin (TCT), a fragment of the bacterial surface molecule peptidoglycan (PGN), is the factor responsible for the extensive tissue damage characteristic of whooping cough and gonorrhea infections. Here, we report that Vibrio fischeri also releases TCT, which acts in synergy with lipopolysaccharide (LPS) to trigger tissue development in its mutualistic symbiosis with the squid Euprymna scolopes. As components of PGN and LPS have commonly been linked with pathogenesis in animals, these findings demonstrate that host interpretation of these bacterial signal molecules is context dependent. Therefore, such differences in interpretation can lead to either inflammation and disease or to the establishment of a mutually beneficial animal-microbe association. 相似文献
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Liu T Liu Z Song C Hu Y Han Z She J Fan F Wang J Jin C Chang J Zhou JM Chai J 《Science (New York, N.Y.)》2012,336(6085):1160-1164
Pattern recognition receptors confer plant resistance to pathogen infection by recognizing the conserved pathogen-associated molecular patterns. The cell surface receptor chitin elicitor receptor kinase 1 of Arabidopsis (AtCERK1) directly binds chitin through its lysine motif (LysM)-containing ectodomain (AtCERK1-ECD) to activate immune responses. The crystal structure that we solved of an AtCERK1-ECD complexed with a chitin pentamer reveals that their interaction is primarily mediated by a LysM and three chitin residues. By acting as a bivalent ligand, a chitin octamer induces AtCERK1-ECD dimerization that is inhibited by shorter chitin oligomers. A mutation attenuating chitin-induced AtCERK1-ECD dimerization or formation of nonproductive AtCERK1 dimer by overexpression of AtCERK1-ECD compromises AtCERK1-mediated signaling in plant cells. Together, our data support the notion that chitin-induced AtCERK1 dimerization is critical for its activation. 相似文献
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Gobert V Gottar M Matskevich AA Rutschmann S Royet J Belvin M Hoffmann JA Ferrandon D 《Science (New York, N.Y.)》2003,302(5653):2126-2130
The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects. 相似文献
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Variable lymphocyte receptors (VLRs) rather than antibodies play the primary role in recognition of antigens in the adaptive immune system of jawless vertebrates. Combinatorial assembly of leucine-rich repeat (LRR) gene segments achieves the required repertoire for antigen recognition. We have determined a crystal structure for a VLR-antigen complex, VLR RBC36 in complex with the H-antigen trisaccharide from human blood type O erythrocytes, at 1.67 angstrom resolution. RBC36 binds the H-trisaccharide on the concave surface of the LRR modules of the solenoid structure where three key hydrophilic residues, multiple van der Waals interactions, and the highly variable insert of the carboxyl-terminal LRR module determine antigen recognition and specificity. The concave surface assembled from the most highly variable regions of the LRRs, along with diversity in the sequence and length of the highly variable insert, can account for the recognition of diverse antigens by VLRs. 相似文献
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目的 探讨液基薄层细胞学检测(TCT)技术在肺癌诊断中的应用价值。方法 收集400例肺癌患者和200例非肺癌患者的痰液、胸腔积液、支气管肺泡灌洗液及支气管刷片共600例,同时进行TCT和传统涂片法(CS)检测,比较两种方法的敏感度和特异度。结果 TCT检测的敏感度为73.0%,特异度为97.5%,CS法检测的敏感度为29.0%,特异度为99.5%,TCT检测的敏感度高于CS法(P<0.05)。TCT法在涂片质量、判断癌细胞形态学方面均较CS法好。TCT分类诊断和病理组织学诊断的总符合率为86.6％。TCT分类诊断和细胞蜡块结合免疫细胞化学诊断的总符合率为89.0％。结论 TCT检测法能明显提高肺癌细胞的阳性检出率,值得推广应用。 相似文献
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Toll-like receptors (TLRs) play key roles in activating immune responses during infection. The human TLR3 ectodomain structure at 2.1 angstroms reveals a large horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs). Asparagines conserved in the 24-residue LRR motif contribute extensive hydrogen-bonding networks for solenoid stabilization. TLR3 is largely masked by carbohydrate, but one face is glycosylation-free, which suggests its potential role in ligand binding and oligomerization. Highly conserved surface residues and a TLR3-specific LRR insertion form a homodimer interface in the crystal, whereas two patches of positively charged residues and a second insertion would provide an appropriate binding site for double-stranded RNA. 相似文献
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Messaoudi I Guevara Patiño JA Dyall R LeMaoult J Nikolich-Zugich J 《Science (New York, N.Y.)》2002,298(5599):1797-1800
Major histocompatibility complex (mhc)-encoded molecules govern immune responses by presenting antigenic peptides to T cells. The extensive polymorphism of genes encoding these molecules is believed to enhance immune defense by broadening the array of antigenic peptides available for T cell recognition, but direct evidence supporting the importance of this mechanism in combating pathogens is limited. Here we link mhc polymorphism-driven diversification of the cytotoxic T lymphocyte (CTL) repertoire to the generation of high-avidity, protective antiviral T cells and to superior antiviral defense. Thus, much of the beneficial effect of the mhc polymorphism in immune defense may be due to its critical influence on the properties of the selected CTL repertoire. 相似文献
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Primary intracellular symbiotes of the pea aphid, Acyrthosiphon pisum (Harris), when fixed with potassium permanganate, revealed a distinctly staining area between the cytoplasmic membrane and the outer cell-wall envelope. This area is thought to be analogous to the peptidoglycan complex of the Eubacteriales. In addition, the diagnostic bacterial peptidoglycan amino compounds, muramic acid and diaminopimelic acid, were detected in a hydrochloric acid hydrolyzate of isolated symbiotes. 相似文献
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20世纪90年代,天然免疫研究升温,成了现代免疫学研究前沿,红细胞天然免疫研究又掀起了新的高潮。红细胞具有许多与免疫有关的物质,它们具有识别、黏附、浓缩、杀伤抗原、清除循环免疫复合物,还参与机体免疫的调控。随着免疫学的不断发展、免疫技术的不断改进,免疫复合物疾病越来越引起临床工作者的重视。本文主要研究红细胞对免疫复合物的调控作用,以及红细胞Ⅰ型补体受体(CR1)在循环免疫复合物清除中的作用机理,阐明红细胞CR1数量与活性的改变对免疫复合物疾病的影响。 相似文献
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Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a quaternary receptor signaling complex containing alpha (IL-2Ralpha), beta (IL-2Rbeta), and common gamma chain (gc) receptors. In the structure of the quaternary ectodomain complex as visualized at a resolution of 2.3 angstroms, the binding of IL-2Ralpha to IL-2 stabilizes a secondary binding site for presentation to IL-2Rbeta. gammac is then recruited to the composite surface formed by the IL-2/IL-2Rbeta complex. Consistent with its role as a shared receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, gammac forms degenerate contacts with IL-2. The structure of gammac provides a rationale for loss-of-function mutations found in patients with X-linked severe combined immunodeficiency diseases (X-SCID). This complex structure provides a framework for other gammac-dependent cytokine-receptor interactions and for the engineering of improved IL-2 therapeutics. 相似文献
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Genetic self-incompatibility in Brassica is determined by alleles of the transmembrane serine-threonine kinase SRK, which functions in the stigma epidermis, and of the cysteine-rich peptide SCR, which functions in pollen. Using tagged versions of SRK and SCR as well as endogenous stigma and pollen proteins, we show that SCR binds the SRK ectodomain and that this binding is allele specific. Thus, SRK and SCR function as a receptor-ligand pair in the recognition of self pollen. Specificity in the self-incompatibility response derives from allele-specific formation of SRK-SCR complexes at the pollen-stigma interface. 相似文献
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Glycosylation and the immune system 总被引：1，自引：0，他引：1
Almost all of the key molecules involved in the innate and adaptive immune response are glycoproteins. In the cellular immune system, specific glycoforms are involved in the folding, quality control, and assembly of peptide-loaded major histocompatibility complex (MHC) antigens and the T cell receptor complex. Although some glycopeptide antigens are presented by the MHC, the generation of peptide antigens from glycoproteins may require enzymatic removal of sugars before the protein can be cleaved. Oligosaccharides attached to glycoproteins in the junction between T cells and antigen-presenting cells help to orient binding faces, provide protease protection, and restrict nonspecific lateral protein-protein interactions. In the humoral immune system, all of the immunoglobulins and most of the complement components are glycosylated. Although a major function for sugars is to contribute to the stability of the proteins to which they are attached, specific glycoforms are involved in recognition events. For example, in rheumatoid arthritis, an autoimmune disease, agalactosylated glycoforms of aggregated immunoglobulin G may induce association with the mannose-binding lectin and contribute to the pathology. 相似文献
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Liu L Botos I Wang Y Leonard JN Shiloach J Segal DM Davies DR 《Science (New York, N.Y.)》2008,320(5874):379-381
Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD does not change upon binding to dsRNA. 相似文献
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髓样分化蛋白-2(Myeloid differentiation protein-2,MD-2)是一种分子量为20～30 kD的分泌蛋白,它结合在Toll样受体4(Tolllike receptor 4,TLR4)胞外区,能与TLR4组成复合体(MD-2/TLR4),在细菌脂多糖(lipopolysaccharide,LPS)的识别及其信号转导中发挥重要作用,MD-2也是目前炎症、感染、免疫等病理过程研究的热点之一。本文对MD-2基因结构、基因表达及MD-2与机体天然免疫等方面研究结果进行综述,以期阐释MD-2的基因与天然免疫的关系,为揭示MD-2基因的功能提供技术参考。 相似文献
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Aricescu AR Siebold C Choudhuri K Chang VT Lu W Davis SJ van der Merwe PA Jones EY 《Science (New York, N.Y.)》2007,317(5842):1217-1220
Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. Human RPTPmu is a type IIB receptor protein tyrosine phosphatase that both forms an adhesive contact itself and is involved in regulating adhesion by dephosphorylating components of cadherin-catenin complexes. Here we describe a 3.1 angstrom crystal structure of the RPTPmu ectodomain that forms a homophilic trans (antiparallel) dimer with an extended and rigid architecture, matching the dimensions of adherens junctions. Cell surface expression of deletion constructs induces intercellular spacings that correlate with the ectodomain length. These data suggest that the RPTPmu ectodomain acts as a distance gauge and plays a key regulatory function, locking the phosphatase to its appropriate functional location. 相似文献
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Hanson MA Roth CB Jo E Griffith MT Scott FL Reinhart G Desale H Clemons B Cahalan SM Schuerer SC Sanna MG Han GW Kuhn P Rosen H Stevens RC 《Science (New York, N.Y.)》2012,335(6070):851-855
The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses. 相似文献