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 A and 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. Crystal structures of influenza A HA at pre- and post-fusion states have been a foundation for our current understanding of HA-mediated viral entry into host cells. However, despite the significant differences of influenza B HA from influenza A HA, structural study of influenza B HA is still lacking. 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, which are distinct from those of influenza A HA. In addition, 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 angstroms (GUP-5637). However, molecular replacement failed to find a solution when using as searching models either the post-fusion structure of influenza A HA, or part of pre-fusion influenza B HA structure that should be preserved in post-fusion state. Therefore, data for heavy-atom derivatives are needed in order to solve the structure of post-fusion influenza B HA.
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