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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.
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Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.

机译:人类免疫缺陷病毒(HIV)抗原:多价人类粘蛋白MUC1-HIV V3嵌合蛋白的结构和血清学。

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摘要

Molecular modeling and two-dimensional NMR techniques enable us to identify structural features in the third variable region (V3) loop of the human immunodeficiency virus (HIV) surface glycoprotein gp120, in particular the principal neutralizing determinant (PND), that remain conserved despite the sequence variation. The conserved structure of the PND is a solvent-accessible protruding motif or a knob, structurally isomorphous with the immunodominant knobs in the tandem repeat protein of human mucin 1 (MUC1) (a tumor antigen for breast, pancreatic, and ovarian cancer). We have replaced the mucin antigenic knobs by the PND knobs of the HIV MN isolate in a set of chimeric human MUC1/HIV V3 antigens. This produced multivalent HIV antigens in which PNDs are located at regular intervals and separated by extended mucin spacers. In this article we show by two-dimensional NMR spectroscopy that the multivalent antigens preserve the PNDs in their native structure. We also demonstrate by ELISA that the antigens correctly present the PNDs for binding to monoclonal antibodies or polyclonal antisera from HIV-infected patients.
机译:分子建模和二维NMR技术使我们能够鉴定人免疫缺陷病毒(HIV)表面糖蛋白gp120的第三可变区(V3)环中的结构特征,尤其是主要中和决定簇(PND),尽管序列变异。 PND的保守结构是溶剂可及的突出基序或纽结,与人粘蛋白1(MUC1)(乳腺癌,胰腺癌和卵巢癌的肿瘤抗原)的串联重复蛋白中的免疫优势纽结在结构上同构。我们已经用一组嵌合人类MUC1 / HIV V3抗原中的HIV MN分离物的PND旋钮代替了粘蛋白抗原旋钮。这产生了多价的HIV抗原,其中PND以规则的间隔定位,并被延伸的粘蛋白间隔子隔开。在本文中,我们通过二维NMR光谱表明,多价抗原将PND保留在其天然结构中。我们还通过ELISA证明了抗原正确地呈现了与来自HIV感染患者的单克隆抗体或多克隆抗血清结合的PND。

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