Fig. 5: Structural topographical classification of FMDV antibodies.

a Cryo-EM structure of FMDV dissociated pentamer (12S) complexed with M3F. The complex is displayed from the outside (left) and inside (middle). Independent M3F epitopes (right) are shown as spheres on 12S and circled in yellow. The viral proteins and M3F are colored as indicated in the bar below, consistent across panels. b, c Detailed interactions between 12S and M3F. Binding residues are shown as sticks, hydrogen bonds as yellow dashed lines, and the hydrophobic pocket in transparent gray. d Structure-based antigenic clustering of FMDV antibodies. A total of 13 FMDV antibodies with available structures, including 12 NAbs and M3F that binds the inner capsid, were clustered into five classes (I, II, III, IV, V). e Superimposition matrix of FMDV antibody structures’ output from epitopes of any two antibodies showing the clustering into five classes. f Footprints of the four NAb classes on FMDV 146S are shown, with lighter colors marking each class (as in panel g) and yellow highlighting the overlapping epitopes of class III and IV NAbs. g Surface representation model showing five classes of FMDV antibodies bound to 146S or 12S, with classes colored as in panel d. h A comparison study of serum expression dominance for representatives from each of the five antibody classes between 146S and 12S immunized pig groups. Data are presented as mean +/– SD of n = 6 biologically independent samples for each group. Source data are provided as a Source Data file. i Footprints of the five antibody classes on adjacent 146S pentamers show specificity for binding at pentamer interfaces or distinct protomers. j Epitopes of three 146S-specific NAbs from classes I (left), III (middle), and IV (right), highlighting the molecular basis for 146S specificity. Epitopes are colored by class. Conformational changes between 146S and 12S for class I NAb M688F are shown by superimposing VP1 from 12S onto 146S (left), comparing epitope of M688F (blue dots) with superimposed 12S (yellow dots). Yellow dots are hidden where they overlap with blue. Epitopes of R55 (middle) and M678F (right) span two adjacent protomers across the pentamer interface.