Vertebrate protein glycosylation: diversity, synthesis and function

Abstract

Contemporary studies of protein glycosylation have revealed numerous examples in which glycan structures attached to proteins and lipids have essential roles in biological recognition events. Glycans have critical functions throughout the cell, from the cytosol and secretory compartments to the cell surface and the extracellular space. Conserved contributions of N-glycan structures in chaperone interactions and protein quality control are initiated co-translationally via the distinctive catalytic mechanism of the oligosaccharyltransferase, and glycan processing continues throughout the dynamic collection of secretory compartments that lead to the cell surface. The complex assortment of glycosylation enzymes comprises an intricate assembly line for glycan maturation from the ER through the Golgi. The localization, dynamics, interactions, regulation and substrate competition of these enzymes within the ER and Golgi remains an active area of study. Of the many roles that glycans have at the cell surface, emerging paradigms have highlighted the importance of protein domain-specific glycosylation in facilitating or modulating biological recognition events. Advances in high-throughput glycan structural analysis are beginning to provide novel insights into correlations with gene expression patterns for glycosylation machinery and genome-wide associations that define global regulation of glycan diversity. The diversity of glycan structures clearly provides an additional level of information content in biological systems, but the challenge for the future lies in identifying how different biological contexts determine glycan encoded functions within the bewildering array of heterogeneous glycan structures.