SOLUTION X-RAY SCATTERING STUDIES ON A PRE-FUSION INTERMEDIATE OF INFLUENZA HEMA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 流感血凝素是一种三聚体糖蛋白，在内吞作用后介导病毒和宿主膜的融合。我们对菠萝酶释放的血凝素进行了溶液小角X射线散射(SAXS)研究。根据SAXS数据重建了中性和中等酸性条件下BHA的三维结构模型。通过将中性pH晶体结构和SAXS形状包络相结合，构建了一个伪原子模型。该模型表明，在早期内体的pH下，HA1球状结构域保持关联，使尖峰看起来基本完整，但HA2亚单位N-末端的融合肽以及HA2的重要相关部分似乎已经重组，并可能面对宿主细胞膜。该模型还表明，由中央HA2螺旋束的一部分形成的疏水核心，以及可能来自HA1亚基的插入环，有助于在融合激活过程中保持棘波的完整性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza hemagglutinin is a trimeric glycoprotein that mediates the fusion of viral and host membranes following endocytosis. We have conducted solution small-angle x-ray scattering (SAXS) studies of bromelain-released hemagglutinin at the pH of early endosomes. Three-dimensional structural models of BHA at neutral and mildly acidic pH were reconstructed from the SAXS data. A pseudoatomic model was constructed by merging the neutral pH crystal structure and SAXS shape envelope. The model suggests that at the pH of early endosomes, the HA1 globular domains remain associated such that the spike appears mostly intact, however the fusion peptide at the N-terminus of the HA2 subunits as well as significant, associated portions of HA2 appear to have reorganized and may be presented to face the host cell membrane. The model also suggests that a hydrophobic core formed by a portion of the central HA2 helical bundle and possibly an inserted loop from the HA1 subunits helps to maintain the integrity of the spike during fusion activation.