Abstract
Understanding glycan structure and dynamics is central to understanding protein-carbohydrate recognition and its role in protein-protein interactions. Given the difficulties in obtaining the glycan's crystal structure in glycoconjugates due to its flexibility and heterogeneity, computational modeling could play an important role in providing glycosylated protein structure models. To address if glycan structures available in the PDB can be used as templates or fragments for glycan modeling, we present a survey of the N-glycan structures of 35 different sequences in the PDB. Our statistical analysis shows that the N-glycan structures found on homologous glycoproteins are significantly conserved compared to the random background, suggesting that N-glycan chains can be confidently modeled with template glycan structures whose parent glycoproteins share sequence similarity. On the other hand, N-glycan structures found on non-homologous glycoproteins do not show significant global structural similarity. Nonetheless, the internal substructures of these N-glycans, particularly, the substructures that are closer to the protein, show significantly similar structures, suggesting that such substructures can be used as fragments in glycan modeling. Increased interactions with protein might be responsible for the restricted conformational space of N-glycan chains. Our results suggest that structure prediction/modeling of N-glycans of glycoconjugates using structure database could be effective and different modeling approaches would be needed depending on the availability of template structures.
Highlights
Glycosylation represents one of the most important posttranslational modifications [1,2] and is ubiquitous in all domains of life
In this work, using the Protein Data Bank (PDB) crystal structures that contain Nglycans, we examined the conformational variability in various Nglycans
Using Glycan Reader [36], an automatic sugar recognition algorithm that we developed, all N-linked glycoprotein structures were obtained from the PDB and sorted by their N-glycan sequence
Summary
Glycosylation represents one of the most important posttranslational modifications [1,2] and is ubiquitous in all domains of life. The glycosylation machinery is largely conserved in eukaryotes, and more than 50% of all eukaryotic proteins are expected to be glycosylated [3,4]. The N-glycosylation pathway is the most common pathway in which an oligosaccharide is covalently attached to the side chain of asparagine [2]. Such an oligosaccharide appendage masks the protein surface, protecting the glycoprotein from degradation and nonspecific protein-protein interactions (reviewed in [5,6,7]). N-glycosylation alters the biophysical properties in the vicinity of the glycosylation site and affects the folding rates and the thermal stability of the protein [8,9]. Some N-linked oligosaccharides (N-glycans) are directly involved in specific molecular recognition events; e.g., lectins and antibodies can recognize specific N-glycans on viral envelope glycoproteins such as HIV gp120 [10,11,12,13]
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