Figure 3: Suboptimal spacing and orientation of epitope pairs makes IgG walk stochastically on antigenic surfaces.
From: IgGs are made for walking on bacterial and viral surfaces
(a) On the binding of one of the two IgG Fab arms to an antigenic epitope the remaining arm can attach adjacent epitopes within a distance of roughly 6–12 nm6,7. (b) The paratopes exhibit twofold symmetry viewed down the IgG’s Fc axes (yellow asterisk). The paratopes intrinsic orientation with respect to the Fab arm represents an additional degree of freedom (projection on the x–y axes; white arrows). Stress-free bivalent binding can be accomplished by binding to an epitope pair schematized by red arrows (orientations of white and red arrows match). In contrast, the epitope pair schematized as black arrows requires adjustment via rotation which might result in tension. (c) Single paratopes, as in the Fabs on the S-layer (Supplementary Fig. 3) can always fully adjust to a given epitope orientation. (d) Accessible epitope pairs on S-layer. Scale bar, 10 nm. (e) Twofold symmetry-related epitopes on S-layer. As we did not observe static bivalent binding, the intrinsic epitope orientations presumably did not match the intrinsic paratope orientation. (f) Dwell time (Fig. 2) of antibody residence on S-layers showed that the single bond lifetime (τ1) of a bivalently bound antibody is reduced when compared with the corresponding monovalently bound Fab. (g) Accessible epitope pairs on PM. (h) PM does not possess any twofold symmetry-related epitopes. Scale bar, 10 nm. (i) Steric strain in bivalent bound anti-Sendai antibodies lowers the energy barrier against thermal activation. (j) Accessible epitope pairs on a streptavidin crystal. Scale bar, 10 nm. (k) 22 2-fold related epitope pairs can be found within the accessible area, only differing in distance and intrinsic epitope orientation (cf. Methods). (l) At least one of these pairs allows for bivalent binding with negligible strain resulting in static bivalent binding (cf. Fig. 2e).
