The Structural Role of Antibody N-Glycosylation in Receptor Interactions.

ABSTRACT: Asparagine(N)297-linked glycosylation of immunoglobulin G (IgG) Fc is required for binding to FcγRIIa, IIb, and IIIa, although it is unclear how it contributes. We found the quaternary structure of glycosylated Fc was indistinguishable from aglycosylated Fc, indicating that N-glycosylation does not maintain relative Fc Cγ2/Cγ3 domain orientation. However, the conformation of the C'E loop, which contains N297, was significantly perturbed in the aglycosylated Fc variant. The conformation of the C'E loop as measured with a range of Fc variants shows a strong correlation with FcγRIIIa affinity. These results indicate that the primary role of the IgG1 Fc N-glycan is to stabilize the C'E loop through intramolecular interactions between carbohydrate and amino acid residues, and preorganize the Fc

SUBMITTER: Subedi GP 

PROVIDER: S-EPMC4558368 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature