Alternative conformations of a major antigenic site on RSV F

Jones, Harrison G.; Battles, Michael B.; Lin, Chun-Chi; Bianchi, Siro; Corti, Davide; McLellan, Jason S.

The coordinates and structure factors for the F-RSD5-GL complex, the unbound AM22 Fab, and the F-AM22 complex, have been deposited in the Protein Data Bank (PDB) under accession codes 6DC3, 6DC4, and 6DC5, respectively. Mann-Whitney U test. (B) SPR sensorgrams demonstrate that parental RSD5-WT has similar binding affinity and kinetics to RSD5-GL. The raw data is plotted as a black line and the fitted curve is shown as a thicker red line. Each binding curve has a 180 second association phase, followed by a 500 second dissociation phase. The equilibrium dissociation constant (K D ) is shown directly above the sensorgram curves, while the association (k a ) and dissociation (k d ) rate constants are shown below the sensorgram. (TIF) S3 Fig. AM22 , RSD5-GL, and D25 do not bind to postfusion RSV F. SPR sensorgrams demonstrate that AM22, RSD5-GL and D25 do not bind to postfusion RSV F derived from (A) subtype A or (B) subtype B. The raw data is plotted as a black line. Motavizumab (Mota) Fab is a conformation-independent antibody and is included as a positive control, and the fitted curve in this sensorgram is shown as a thicker red line. Each binding curve has a 180 second association phase, followed by a 500 second dissociation phase. (TIF) S4 Fig. AM22 binds with decreased affinity to subtype A prefusion RSV F with a K209Q substitution. SPR sensorgram of AM22 Fab binding to subtype A prefusion RSV F with a K209Q substitution. The raw data is plotted as a black line and the fitted curve used to calculate the binding kinetics is plotted as a thicker red line. Each binding curve has a 180 second association phase, followed by a 500 second dissociation phase. The equilibrium dissociation constant (K D ) is displayed immediately above the SPR curve. The association rate constant (k a ) and dissociation rate constant (k d ) are shown below the sensorgram.