ANTIGENIC STRUCTURE AND VARIATION IN AN INFLUENZA VIRUS-N9 NEURAMINIDASE
ANTIGENIC STRUCTURE AND VARIATION IN AN INFLUENZA VIRUS-N9 NEURAMINIDASE
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DOI：
10.1128/jvi.61.9.2910-2916.1987
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发表时间：
1987-09-01
影响因子：
5.4
通讯作者：
LAVER, WG
中科院分区：
文献类型：
--
作者：
WEBSTER, RG;AIR, GM;LAVER, WG
我们先前通过x射线晶体学确定了流感病毒N9神经氨酸苷酶（NA）与单克隆抗体NC-41 Fab片段之间复合物的三维结构。M. coleman， W. G. Laver， J. N. Varghese， A. T. Baker，。张建军，张建军，张建军，《自然科学》（英文版），326:358-363,1987]。该抗体与Na蛋白上表面的一个表位结合，该表位由四个多肽环组成，面积约为600 . ang2(60 nm2)。我们现在描述了NC-41和其他N9 NA单克隆抗体的特性，以及用这些抗体选择的变体（逃逸突变体）的特性。除1个外，所有逃逸突变体都有单氨基酸序列变化，影响了NC-41的结合，因此位于NC-41表位内。另一个抗原表位外发生了变化，但不影响其他抗体的结合。所有选择变异体的抗体都以胎蛋白（分子量，50,000）为底物抑制酶活性，但只有5种抗体，包括NC-41，也以小底物n-乙酰神经胺-乳糖（分子量，600）抑制酶活性。这五种可能通过扭曲NA的催化位点来抑制酶的活性。分离的，完整的N9 NA分子在没有洗涤剂的情况下形成玫瑰花，这些具有高水平的血凝素活性（W. G. Laver， P. M. Colman， R. G. Webster， V. S. Hinshaw和G. M. Air，病毒学137:314-323,1984）。2-脱氧-2,3-脱氢- n -乙酰神经氨酸能有效抑制N9 Na的酶活性，而血凝素活性不受影响。NC-41表位序列改变的几个变异的NAs失去了血凝素活性，但没有任何酶活性的损失，这表明这两种活性与N9 NA头部的不同位点有关。
We previously determined, by X-ray crystallography, the three-dimensional structure of a complex between influenza virus N9 neuraminidase (NA) and the Fab fragments of monoclonal antibody NC-41 [P. M. Colman, W. G. Laver, J. N. Varghese, A. T. Baker,. P. A. Tulloch, G. M. Air, and R. G. Webster, Nature (London) 326:358-363, 1987]. This antibody binds to an epitope on the upper surface of the Na which is made up of four polypeptide loops over an area of approximately 600 .ANG.2 (60 nm2). We now describe properties of NC-41 and other monoclonal antibodies to N9 NA and the properties of variants selected with these antibodies (escape mutants). All except one of the escape mutants had single amino acid sequence changes which affected the binding of NC-41 and which therefore are located within the NC-41 epitope. The other one had a change outside the epitope which did not affect the binding of any of the other antibodies. All the antibodies which selected variants inhibited enzyme activity with fetuin (molecular weight, 50,000) as the substrate, but only five, including NC-41, also inhibited enzyme activity with the small substrate N-acetylneuramin-lactose (molecular weight, 600). These five probably inhibited enzyme activity by distorting the catalytic site of the NA. Isolated, intact N9 NA molecules form rosettes in the absence of detergent, and these possess high levels of hemagglutinin activity (W. G. Laver, P. M. Colman, R. G. Webster, V. S. Hinshaw, and G. M. Air, Virology 137:314-323, 1984). The enzyme activity of N9 Na was inhibited efficiently by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, whereas hemagglutinin activity was unaffected. The NAs of several variants with sequence changes in the NC-41 epitope lost hemagglutinin activity without any loss of enzyme activity, suggesting that the two activities are associated with separate sites on the N9 NA head.