Here, combining X-ray crystallography, cryo-electron tomography and animal studies, the authors show that the monoclonal antibody against Ebola virus glycoprotein (GP1,2) 3A6 exerts protection via binds to a conformation of GP1,2 that is lifted from the virion membrane, providing insights into the mechanism of action with implications for the design of anti-Ebola therapeutics. The gene discussed is ART4; the disease is Ebola hemorrhagic fever.