Mutation of Y407 in the CH3 domain dramatically alters glycosylation and structure of human IgG.

ABSTRACT: Antibody engineering is increasingly being used to influence the properties of monoclonal antibodies to improve their biotherapeutic potential. One important aspect of this is the modulation of glycosylation as a strategy to improve efficacy. Here, we describe mutations of Y407 in the CH3 domain of IgG1 and IgG4 that significantly increase sialylation, galactosylation, and branching of the N-linked glycans in the CH2 domain. These mutations also promote the formation of monomeric assemblies (one heavy-light chain pair). Hydrogen-deuterium exchange mass spectrometry was used to probe conformational changes in IgG1-Y407E, revealing, as expected, a more exposed CH3-CH3 dimerization interface. Additionally, allosteric structural effects in the CH2 domain and in the CH2-CH3 interface were ident

SUBMITTER: Rose RJ 

PROVIDER: S-EPMC3893232 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature