Fig. 3: F12 binds the CD of the 229E S protein and lacks cross-neutralizing activity to NL63.
From: Antigenic mapping reveals sites of vulnerability on α-HCoV spike protein
a F12-dependent amide hydrogen protection indicates its potential interacting regions in 229E S2. S2 segments that manifested considerable HDX decrease at all measured timepoints in the presence of Fab F12 are highlighted with dark green on the cartoon representation of one 229E S protomer (S2 colored purple) in the context of 229E S trimer (light gray surface presentation). Deuterium uptake plots of these segments in the absence (black) and presence (dark green) of Fab F12 are plotted as percent deuterium uptake versus time on a logarithmic scale to illustrate their HDX kinetics. b Model of Fab F12 binding to 229E S trimer in the all-RBD-down state. Fab F12 is depicted as ribbons (light and heavy chains in different shades of magenta). The authentic epitope of F12 as double-defined by HDX-MS results and mutagenesis verification is highlighted with dark green on the gray surface representation of 229E S trimer. c To examine the correspondence between cryo-EM 2D class averages and the model of F12-bound 229E S trimer, representative 2D projections of the model (left panels) is compared to reference-free averages of F12-bound 229E S trimer (middle panels) or 229E S trimer alone (right panels). d Sequence alignment of CD and stem helix region within the S2 subunits of α- and β-HCoVs. The structural epitope of F12 and the epitopes of other previously reported S2-directed antibodies are indicated with solid lines under the alignment.
