Structural basis of 101F cross-reactivity.

Abstract

<p><b>A</b>) <i>Left</i>: Superposition of the linear 101F epitope derived from the hMPV (white) and hRSV (blue) postfusion F proteins. Side-chains are shown as sticks, with oxygen atoms colored red and nitrogen atoms colored blue. hMPV F residues are labeled and numbered. <i>Right</i>: Model of mAb 101F bound to antigenic site IV derived from the hMPV and hRSV postfusion F proteins. 101F heavy chain is colored red and light chain is yellow. <i>Bottom</i>: Sequence alignment of the antigenic site IV domain from hMPV and hRSV F. Identical residues have white text with black backgrounds, whereas residues that are similar are in bold and have a black border. Open circles denote residues with >10 Ų buried surface area and filled rectangles denote residues whose side-chains form hydrogen bonds with 101F in the hRSV F peptide-bound crystal structure (PDBID: 3O45). <b>B</b>) Negatively stained electron micrographs of 101F Fab bound to postfusion hRSV F and hMPV F. The top two panels are 2D averages whereas the other panels are examples of individual negatively stained F–Fab complexes. <b>C</b>) Models of a single 101F Fab in complex with postfusion F trimers of hRSV and hMPV. Molecular surfaces of the trimers are shown, and residues within 5.5 Å of 101F atoms are darker.</p