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 (flu) viruses have three subtypes, A, B and C. Among them, A and B 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 have been obtained for flu A HA at both pre- and post-fusion states, which have been a foundation for our current understanding of the viral entry by a number of enveloped viruses including HIV and Ebola virus. Crystal structure of flu C HEF (equivalent to HA) at pre-fusion state has also been determined, which has shed new light on the evolution of flu viruses. However, the structures of flu B HA at pre-fusion and post-fusion states, as well as flu C HEF at post-fusion state, are still lacking. Our group has successfully solved the crystal structures of flu B HA at pre-fusion state in un-liganded 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 flu B HA and into its antigenic variation and receptor binding, which are distinct from that of flu A HA. Following that, we have invested considerable efforts to growing the crystals of flu B HA and C HEF at low-pH, post-fusion state. Their high-resolution structures, in comparison with that of flu A HA at post-fusion state, will provide critical information regarding the large-scale conformational change of HA and the possible energetics for HA-induced membrane fusion. These structures will also complete the structural studies of flu viruses, for three different subtypes (A, B and C) and at two distinct states (pre- and post-fusion). Most recently, we have successfully obtained the crystals of flu B and C HAs at low-pH, post-fusion state. Crystals of flu B HA are single plates, and those of flu C HEF are single but small cubes with a dimension of 70x70x70 microns.
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| Pfoh, Roland; Pai, Emil F; Saridakis, Vivian (2015) Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides. Acta Crystallogr D Biol Crystallogr 71:2032-9 |
| Mariette, Céline; Guérin, Laurent; Rabiller, Philippe et al. (2015) The creation of modulated monoclinic aperiodic composites in n-alkane/urea compounds. Z Kristallogr Cryst Mater 230:5-11 |
| Yang, Xiaojing; Stojkovi?, Emina A; Ozarowski, Wesley B et al. (2015) Light Signaling Mechanism of Two Tandem Bacteriophytochromes. Structure 23:1179-89 |
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