A molecular basis for glycosylation-induced conformational switching

Abstract

Background: Asparagine-linked glycosylation has the capacity to greatly influence the structure and function of glycoproteins. In most cases, however, it is unclear specifically how the carbohydrate moiety interacts with the protein to influence its conformation.

Results: A series of glycosylation based on the critical A285 glycosylation site of the hemagglutinin glycoprotein from influenza from influenza virus was used as a model system to study the effects of asparagine-linked glycosylation. Derivatization of this peptide with a family of short carbohydrates reveals that subtle changes in the structure of the carbohydrate have a dramatic impact on peptide conformation. Modification of the hemagglutinin glycopeptide with a truncated version of the native carbohydrate induces a beta-turn structure similar to the structure found in the native protein. Replacement of the C2 and C2' N-acetyl groups of the carbohydrates with hydroxyl moieties results in a less well-ordered peptide conformation.

Conclusions: It is likely that the N-acetyl groups of the carbohydrates have a critical role in promoting the more compact beta-turn conformation through steric interactions with the peptide. This study has demonstrated that relatively small changes in carbohydrate composition can have dramatic ramifications on glycopeptide conformation.