Figure 4

Structural basis for inhibition of the interaction between IgE-Fc and FcεRI by 8D6. (a) The Cε3 domains in the 8D6 Fab/IgE-Fc complex (light blue) adopt a closed conformation, precluding simultaneous engagement of both sub-sites on sFcεRIα. The 8D6 Fab/IgE-Fc complex and sFcεRIα/IgE-Fc complex (pink)19 structures were superposed on Cε4 domain Cα atoms. (b) When the 8D6 Fab/IgE-Fc and IgE-Fc/sFcεRIα complex structures are superposed on the Cε3 domain which engages FcεRIα at sub-site 1, one Fab (dark blue) and the (Cε2)2 domain pair (light blue) from the 8D6 Fab/IgE-Fc complex clash with sFcεRIα (pink). For clarity, IgE-Fc from the IgE-Fc/sFcεRIα complex is not shown. (c) When the 8D6 Fab/IgE-Fc and IgE-Fc/sFcεRIα complex structures are superposed on the Cε3 domain which engages FcεRIα at sub-site 2, one Fab (dark blue) and the (Cε2)2 domain pair from the 8D6 Fab/IgE-Fc complex (light blue) clash with sFcεRIα (pink). For clarity, IgE-Fc from the IgE-Fc/sFcεRIα complex is not shown.