利用流感血凝素膜融合活性所需构象转变的双突变体进行的研究。
Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity.
作者信息
Steinhauer D A, Martín J, Lin Y P, Wharton S A, Oldstone M B, Skehel J J, Wiley D C
机构信息
National Institute for Medical Research, Mill Hill, London, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12873-8. doi: 10.1073/pnas.93.23.12873.
Abstract
Amino acid substitutions widely distributed throughout the influenza hemagglutinin (HA) influence the pH of its membrane fusion activity. We have combined a number of these substitutions in double mutants and determined the effects on the pH of fusion and on the pH at which the refolding of HA required for fusion occurs. By analyzing combinations of mutations in three regions of the metastable neutral-pH HA that are rearranged at fusion pH we obtain evidence for both additive and nonadditive effects and for an apparent order of dominance in the effects of amino acid substitutions in particular regions on the pH of fusion. We conclude that there are at least three components in the structural transition required for membrane fusion activity and consider possible pathways for the transition in relation to the known differences between neutral and fusion pH HA structures.
摘要
广泛分布于流感血凝素（HA）中的氨基酸替换会影响其膜融合活性的pH值。我们将其中一些替换组合在双突变体中，并确定了其对融合pH值以及融合所需HA重折叠发生时的pH值的影响。通过分析在融合pH值下发生重排的亚稳中性pH值HA三个区域中的突变组合，我们获得了关于加性和非加性效应的证据，以及特定区域氨基酸替换对融合pH值影响的明显优势顺序。我们得出结论，膜融合活性所需的结构转变中至少有三个组成部分，并结合中性和融合pH值HA结构之间的已知差异考虑了可能的转变途径。
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