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

流感HEMA融合前中间体的溶液X射线散射研究

• 批准号: 7954203
• 负责人: HIROTSUGU TSURUTA
• 金额: $ 0.04万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954203
• 关键词: Cell membrane; Computer Retrieval of Information on Scientific Projects Database; Data; Early Endosome; Endocytosis; Face; Funding; Glycoproteins; Grant; Hemagglutinin; Influenza; Influenza Hemagglutinin; Institution; Mediating; Membrane; Modeling; Peptides; Research; Research Personnel; Resources; Roentgen Rays; Shapes; Solutions; Source; Structural Models; Structure; United States National Institutes of Health; Viral; structural biology; synchrotron radiation

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 流感病毒血凝素是一种三聚体糖蛋白，在胞吞作用后介导病毒和宿主细胞膜的融合。我们对早期核内体pH值下菠萝蛋白酶释放的血凝素进行了溶液小角X射线散射（SAXS）研究。从SAXS数据重建了BHA在中性和弱酸性pH下的三维结构模型。将中性pH晶体结构与SAXS形状包络相结合，建立了一个赝原子模型。该模型表明，在早期内体的pH值下，HA 1球状结构域保持缔合，使得刺突似乎大部分是完整的，然而，HA 2亚基的N-末端处的融合肽以及HA 2的显著缔合部分似乎已经重组，并且可能呈现为面向宿主细胞膜。该模型还表明，由中央HA 2螺旋束的一部分和可能的插入环从HA 1亚基形成的疏水核心有助于在融合激活过程中保持穗的完整性。