A structural characterization of protein-carbohydrate interactions
Thieker, David Forrest
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Although carbohydrates are most commonly associated with metabolism, these molecules are involved in a variety of other critical processes that range from cellular trafficking to transcriptional regulation. Alterations in carbohydrate sequence are linked to a host of diseases ranging from cancer to dementia, yet progress in structural glycobiology has been slow compared to that of proteins and DNA. The following work pushes the boundary of our understanding of carbohydrate interactions at the atomic level. First, a 3D adaptation of the Symbol Nomenclature for Glycans (SNFG) was developed as a cartoon representation for carbohydrates to improve the communication of complex structural features to both glycobiologists and non-specialists. Second, the prediction of protein-carbohydrate complexes was improved by including a scoring term within docking programs that accounts for the linkage between glycan residues. Third, the crystal structure of a silayltransferase is presented with a docked model for the sugar donor. Fourth, a significant binding preference was identified between an enzyme within the heparan sulfate biosynthetic pathway and downstream products, with implications for protein localization in vivo. Lastly, a study of the intra-molecular interactions of a glycoprotein suggests a regulatory mechanism in which glycosylation affects intrinsic protein dynamics. Collectively, these efforts contribute to our understanding of the glycan structure-function relationship and facilitate future efforts in glycobiology.