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首页> 外文期刊>Journal of Molecular Biology >INTERACTION OF THE RECEPTOR BINDING DOMAINS OF PSEUDOMONAS AERUGINOSA PILI STRAINS PAK, PAO, KB7 AND P1 TO A CROSS-REACTIVE ANTIBODY AND RECEPTOR ANALOG - IMPLICATIONS FOR SYNTHETIC VACCINE DESIGN
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INTERACTION OF THE RECEPTOR BINDING DOMAINS OF PSEUDOMONAS AERUGINOSA PILI STRAINS PAK, PAO, KB7 AND P1 TO A CROSS-REACTIVE ANTIBODY AND RECEPTOR ANALOG - IMPLICATIONS FOR SYNTHETIC VACCINE DESIGN

机译：假单胞菌铜绿假单胞菌PAK，PAO，KB7和P1的受体结合域与交叉抗体和受体类似物的相互作用-对合成疫苗设计的意义

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The four synthetic peptide antigens, PAK 128-144, PAO 128-144, KB7 128-144 and P1 126-148, correspond in amino acid sequence to the C-terminal receptor binding regions of four strains (PAK, PAO, KB7, P1) of Pseudomonas aeruginosa pilin. The NMR solution structures of the trans forms of the peptides show conserved beta-turns which have been implicated in antibody and receptor recognition. The interactions between these peptides and a cross-reactive monoclonal antibody, PAK-13, have been studied using two-dimensional H-1 NMR spectroscopy in order to map the antigenic determinants recognized by the antibody. Residues for which spectral changes were observed upon antibody binding differed from peptide to peptide but were mostly confined to one or both of the turn regions and to the hydrophobic pockets. Conformational changes in the beta-turns and hydrophobic pockets of these peptides upon antibody binding were also monitored by examination of the pattern of nuclear Overhauser effects (NOEs) versus transferred nuclear Overhauser effects (TRNOEs) for the free versus the bound peptides. Although TRNOEs developed strongly between side chain resonances in the hydrophobic pockets of the peptides, no additional backbone TRNOEs were observed in the presence of antibody, suggesting no major conformational changes in the secondary structures of the peptides upon binding. This implies a flexible antibody combining site, a feature which is discussed with respect to cross-reactivity, strain specificity, and the design of a synthetic peptide vaccine effective against a broad spectrum of P. aeruginosa strains. The binding of the PAK peptide to a disaccharide receptor analog, (beta GalNAc(1-4)beta Gal), was also studied using H-1 NMR in order to map the ''adhesintope'' recognized by the receptor. Spectral changes observed in the peptide spectrum with the binding of receptor were similar to those seen for the binding of antibody, suggesting that the epitope recognized by the antibody is structurally coincident with the adhesintope recognized by the receptor. The relevancy of this result is discussed with respect to immunogenicity versus pathogenicity, and the proper design of a vaccine which could prevent the mutational escape of the pathogen away from the host's defence systems. (C) 1997 Academic Press Limited. [References: 67]
机译：四种合成肽抗原PAK 128-144，PAO 128-144，KB7 128-144和P1 126-148在氨基酸序列上对应于四种菌株（PAK，PAO，KB7，P1 ）的铜绿假单胞菌菌毛。肽反式的NMR溶液结构显示出保守的β-转角，与抗体和受体识别有关。为了绘制抗体识别的抗原决定簇，已使用二维H-1 NMR光谱研究了这些肽与交叉反应性单克隆抗体PAK-13之间的相互作用。抗体结合后观察到光谱变化的残基在肽与肽之间有所不同，但主要限于一个或两个转向区域以及疏水性口袋。还通过检查游离肽与结合肽的核Overhauser效应（NOEs）与转移核Overhauser效应（TRNOEs）的模式，来监测抗体结合后这些肽的β-转角和疏水口袋的构象变化。尽管TRNOE在肽的疏水性口袋中的侧链共振之间强烈发展，但在抗体存在下未观察到其他骨架TRNOE，这表明结合后肽的二级结构没有重大构象变化。这暗示了灵活的抗体结合位点，这是关于交叉反应性，菌株特异性和针对广谱铜绿假单胞菌菌株有效的合成肽疫苗的设计所讨论的特征。还使用H-1 NMR研究了PAK肽与二糖受体类似物（βGalNAc（1-4）beta Gal）的结合，以绘制该受体识别的“粘附位”。在肽光谱中观察到的与受体结合的光谱变化与对抗体结合观察到的光谱变化相似，这表明抗体识别的表位与受体识别的粘附位在结构上重合。讨论了该结果的相关性，包括免疫原性与致病性，以及疫苗的正确设计，可以防止病原体从宿主防御系统逃脱。 （C）1997 Academic Press Limited。 [参考：67]

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