Fig. 3.

Structural changes upon glycosylation of IgG Fc fragments. (A) Schematic view of the principal glycosylation structures attached to Asn297 in the Fc fragment including the respective linkage. Gray shaded parts of the carbohydrate moiety are not displayed in the cartoon. (B) Cartoon of the proposed structural changes within the Fc fragment upon sialylation. The nongalactosylated (G0F) Fc-fragment (top) maintains an open conformation that allows the binding of FcγRs and precludes binding of DC-SIGN or CD23. In the fully α2,6-sialylated Fc (G2FS2), the α1,3-arm (orange/blue) associates with the protein core of the Cγ2 domain, inducing a closed conformation. The resulting closed conformation of the Fc fragment with a changed tertiary structure reveals the binding site for DC-SIGN, whereas that for FcγRs is blocked. The coloring of the carbohydrate moiety is according to the schematic view in A. (C, Upper) Front view of the Fc fragment with the individual domains colored separately with CHOs of the G0F form (PDB code 3AVE). (C, Lower) Front view of the model of fully sialylated Fc (G2FS2) with DC-SIGN bound to it. The coloring of the domains is according to the Fc fragment at top. The right side shows the top view of the respective structures.