GLYCOSYLATION - HETEROGENEITY AND THE 3D STRUCTURE OF PROTEINS

Glycoproteins generally exist as populations of glycosylated variants (glycoforms) of a single polypeptide. Although the same glycosylation machinery is available to all proteins that enter the secretory pathwa y in a given cell, most glycoproteins emerge with characteristic glyco sylation patterns and heterogeneous populations of glycans at each gly cosylation site. The factors that control the composition of the glyco form populations and the role that heterogeneity plays in the function of glycoproteins are important questions for glycobiology. A full und erstanding of the implications of glycosylation for the structure and function of a protein can only be reached when a glycoprotein is viewe d as a single entity. Individual glycoproteins, by virtue of their uni que structures, can selectively control their own glycosylation by mod ulating interactions with the glycosylating enzymes in the cell. Examp les include protein-specific glycosylation within the immunoglobulins and immunoglobulin superfamily and site-specific processing in ribonuc lease, Thy-1, IgG, tissue plasminogen activator, and influenza A hemag glutinin. General roles for the range of sugars on glycoproteins such as the leukocyte antigens include orientating the molecules on the cel l surface. A major role for specific sugars is in recognition by lecti ns, including chaperones involved in protein folding. In addition, the recognition of identical motifs in different glycans allows a heterog eneous population of glycoforms to participate in specific biological interactions.