Hemagglutnin (HA) mediates entry of influenza virus through a series of conformational changes triggered by the low pH of the endosome. The residue or combination of residues acting as pH sensors has not yet been fully elucidated. In this work, we assay pH effects on the structure of H5 HA by soaking HA crystallized at pH 6.5 in a series of buffers with lower pH, mimicking the conditions of the endosome. We find that HA1-H38, which is conserved in Group 1 HA, undergoes a striking change in side chain conformation, which we attribute to its protonation and cation-cation repulsion with conserved HA1-H18. This work suggests that x-ray crystallography can be applied for studying small-scale pH-induced conformational changes providing valuable information on the location of pH sensors in HA. Importantly, the observed change in HA1-H38 conformation is further evidence that the pH-induced conformational changes of HA are the result of a series of protonation events to conserved and non-conserved pH sensors.

中文翻译：

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使用X射线晶体学鉴定流感血凝素中的pH传感器。

血凝素（HA）通过内体低pH引发的一系列构象变化介导流感病毒的进入。尚未完全阐明充当pH传感器的残基或残基组合。在这项工作中，我们通过将结晶于pH 6.5的HA浸泡在一系列pH值较低的缓冲液中（模仿内体的条件），来分析pH对H5 HA结构的影响。我们发现，在第1组HA中保守的HA1-H38在侧链构象上发生了惊人的变化，这归因于它的质子化和与保守的HA1-H18的阳离子排斥。这项工作表明，x射线晶体学可以用于研究小规模的pH诱导的构象变化，从而提供有关HA中pH传感器位置的宝贵信息。重要的，