DETERMINING THE STRUCTURE OF INFLUENZA B VIRUS HEMAGGLUTININ AT POST-FUSION S

确定融合后 B 型流感病毒血凝素的结构

• 批准号: 7726018
• 负责人: QINGHUA WANG
• 金额: $ 0.79万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726018
• 关键词: Antigenic Variation; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; Data; Funding; Grant; Hemagglutinin; Human; Influenza; Influenza B virus; Institution; Mediating; Membrane Fusion; Molecular Structure; Process; Research; Research Personnel; Resources; Roentgen Rays; Source; Structure; Synchrotrons; United States National Institutes of Health; Virus; insight; pathogen; receptor; receptor binding

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 B viruses are important pathogens in human. They gain entrance into host cells via a membrane fusion process mediated by hemagglutinin (HA). This process involves a large conformational change of HA, from neutral-pH, pre-fusion state to low-pH post-fusion state. Our group has successfully determined the crystal structures of influenza B HA at pre-fusion state in unliganded state, as well as in complexes with two receptors of different linkages (GUP-5050). That study has yielded important insights into pre-fusion state structures of influenza B HA and into its antigenic variation and receptor binding. The last piece of missing information is of the low-pH structure of influenza B HA. In the past, we have also obtained the crystals of influenza B HA at post-fusion state. A complete set of diffraction data has been collected to 1.88 ¿ (GUP-5637). However, the crystals suffered from contamination of small crystals so that we were unable to solve the structures by molecular replacement or heavy-atom derivatives. After extensive trials, we have now succeeded in growing crystals of low-pH influenza B HA in different conditions. These crystals gave good diffractions up to 4 angstroms at local X-ray sources. So the use of a synchrotron X-ray source is needed to collect diffraction data for atomic structure determination.

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。 B型流感病毒是人类重要的病原体。它们通过血凝素（HA）介导的膜融合过程进入宿主细胞。该过程涉及HA从中性pH、融合前状态到低pH融合后状态的大的构象变化。 我们的小组已经成功地确定了在未配体状态下的融合前状态的流感B HA的晶体结构，以及在与两种不同键合的受体（GUP-5050）的复合物中的晶体结构。该研究对流感B HA的融合前状态结构及其抗原变异和受体结合产生了重要的见解。最后一个缺失的信息是B型流感HA的低pH结构。 在过去，我们还获得了融合后状态的流感病毒B HA晶体。已收集到一组完整的衍射数据，精确到1.88 <$（GUP-5637）。然而，晶体遭受污染的小晶体，使我们无法解决的结构，分子置换或重原子衍生物。 经过广泛的试验，我们现在已经成功地在不同的条件下生长低pH值的流感B HA晶体。这些晶体在局部X射线源处产生高达4埃的良好衍射。因此，需要使用同步加速器X射线源来收集衍射数据以确定原子结构。