Henipavirus structure and genome organization and models of the G and F glycoprotein soluble ectodomains, Hendra virus (HeV-sG) and Nipah virus (NiV-sF), respectively, and their complexes with respective NiV and HeV cross-reactive neutralizing monoclonal antibodies m102.3 (anti-G) and 5B3 (anti-F). (a) Schematic representation of a henipavirus particle with the structural proteins depicted in different colors (left) and the henipavirus genome (right). HeV and NiV P genes encode 3 nonstructural proteins: The C protein is expressed from an alternative start site, and the V and W proteins are expressed following the addition of one or two G residues at the messenger RNA editing site, respectively (right). (b, left) HeV-sG shown as a dimer solvent-accessible surface view with one monomer (cyan) overlaid with the monoclonal antibody m102.3 CDR-H3 loop (red) at the receptor binding site, and the other monomer (magenta) in complex with m102.3 Fab, which has an identical heavy chain and a similar light chain, that was used in place of the m102.4 monoclonal antibody (mAb) in the structural solution of the complex (109). The HeV-sG consists of amino acids 76–604, and the structures of the two globular head domains of HeV-sG are derived from the crystal structure (103, 172). The stalk regions of each G monomer (residues 77–136) are modeled (173). The light chain of m102.3 Fab is colored in yellow, and the heavy chain is colored in red. (b, middle) The HeV-sG tetramer surface view is modeled with one dimer (cyan and magenta) in front and the other dimer (blue and green) in back. N-linked glycans are gray spheres. (b, right) Structural model of the NiV-sF trimer in complex with the 5B3 Fab derived from the cryo–electron microscopy structure (110). The NiV-sF consists of amino acid residues 1–494 with a FLAG tag (DYKDDDK) introduced between residues L104-V105 and a C-terminal GCN4 motif. Each monomer of NiV-sF is in a different shade of blue, 5B3 heavy chain is in red, and light chain is in gold. N-linked glycans are illustrated in gray.