Grafting of the RSV palavizumab/motavizumab epitope onto the HMPV F protein.

<p>(a) Structures of pre- and post-fusion RSV F highlighting the helix-turn-helix motif for palivizumab and motavizumab. The protein surface and ribbon are colored cyan with the epitope region in each subunit of the trimer colored blue (arrows). (b) Structure of the motavizumab:RSV peptide complex (RCSB code: 3IXT) superimposed on the partial HMPV F structure (RCSB code: 4DAG). Residues from RSV are labeled in black and those of HMPV F are in parentheses and labeled in blue. Residues highlighted with the yellow background were substituted in the RPM-1 mutant. (c) Sequence alignment of RSV and HMPV F proteins, spanning the motavizumab epitope, along with the RPM-1 mutant sequence. Yellow and red boxes highlight amino acids that contact motavizumab, with red indicating less accessible residues of the epitope. Letters above (H/L) the sequences represent contacts with the heavy of light chain CDRs of the motavizumab Fab. Letters below the RPM-1 mutant represent contact residues that were either changed (C), left unchanged (-) or are identical (.) in RSV and HMPV F. (d) Contact map of motavizumab:RSV F peptide contacts from the crystal structure, with RSV residues highlighted in yellow and antibody residues highlighted in green (heavy chain) or blue (light chain). Three residues (L258, N262, N268) are highlighted as making the most contacts per residue across the interface.