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. An unusual feature of the Ebola virus is that products of the viral glycoprotein gene occur in at least two different structural forms. Importantly, the different structures cause the proteins to have different roles in pathogenesis. A trimeric viral surface form is the structure relevant for viral infection and antibody neutralization, while a secreted, dimeric form of the glycoprotein seems to be a preferential target of antibodies. We are raising antibodies against all forms of these proteins, and solving crystal structures of the glycoproteins alone and in complex with these antibodies. These structures will illustrate which epitopes shared between the structures or unique to the viral surface structure lead to effective neutralization of the virus, and will also illustrate how a shared protein sequence can form two separate structures with separate functions in pathogenesis. Additional efforts in the lab include structural analysis of the glycoproteins from the related Marburg virus and also from strains of the dengue virus that have been linked to recent outbreaks of dengue hemorrhagic fever.