Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin
Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin
复制标题
流感病毒血凝素抗原突变体的三维结构
作者：
Marcel Knossow;R. Daniels;A. Douglas;J. Skehel;D. Wiley
流感病毒血凝素 (HA) 糖蛋白的抗原变异与人类呼吸道疾病的反复流行有关（综述参见参考文献 1）。我们通过确定含有单个氨基酸取代的抗原突变体的HA的三维结构，检查了改变HA抗原性所需的结构变化的大小，该突变体是通过在单克隆抗体存在下病毒的生长而选择的。在这里，我们提供的证据表明，简单添加氨基酸侧链仅导致 HA 结构的轻微局部扭曲，足以使病毒逃避单克隆抗体的中和作用。我们的结果还表明，单个氨基酸取代只能引起 HA 结构的局部变化，验证了多项研究中对 HA2-5 和其他分子 6,7 上的抗原位点进行定位的假设，并表明在这种情况下不需要通过大的构象变化来解释 HA 抗原性的变化。变异抗原的结构已被独立成功预测（M. Karplus，个人通讯）。
Antigenic variation in the haemagglutinin (HA) glycoprotein of influenza virus is associated with recurrent epidemics of respiratory disease in man (for review see ref. 1). We have examined the size of structural changes necessary to alter the antigenicity of HA by determining the three-dimensional structure of the HA from an antigenic mutant containing a single amino acid substitution which was selected by growth of virus in the presence of monoclonal antibodies. Here we present evidence that the simple addition of an amino acid side chain which results in only minor local distortions of the structure of the HA is sufficient structural alteration for a virus to escape neutralization by a monoclonal antibody. Our results also demonstrate that single amino acid substitutions can cause only local changes in the HA structure, verifying the assumption made in several studies to locate antigenic sites on the HA2–5 and other molecules6,7 and indicate that proposals8,9 of large conformational changes to account for variations in HA antigenicity are unnecessary in this case. The structure of the variant antigen has independently been successfully predicted (M. Karplus, personal communication).
影响因子：
3.8
作者：
DANIELS, RS;DOUGLAS, AR;WILEY, DC
通讯作者：
WILEY, DC