8.A.46 The Glycan-binding Protein (SusD) Family
Bacteroides thetaiotaomicron, a gram-negative obligate anaerobe, utilizes polysaccharides by binding them to its cell surface and allowing cell-associated enzymes to hydrolyze them into digestible fragments. Reeves et al. 1997 used the starch utilization system as a model to analyze the initial steps involved in polysaccharide binding and breakdown. 14C-Starch binding assays showed that SusC and SusD both contribute to starch binding, that SusC and SusD interact in the outer membrane, and that they are exposed to the cell surface.
Koropatkin et al. 2009 presented the atomic structure of the B. thetaiotaomicron protein BT1043, an outer membrane lipoprotein involved in host glycan metabolism that is a structural homologue of the B. thetaiotaomicron starch-binding protein SusD. Both structures are dominated by tetratrico peptide repeats that may facilitate association with outer membrane beta-barrel transporters required for glycan uptake. The structure of BT1043 complexed with N-acetyllactosamine revealed that recognition is mediated via hydrogen bonding interactions with the reducing end of beta-N-acetylglucosamine, suggesting a role in binding glycans liberated from the mucin polypeptide. The glycan-binding pocket of BT1043 suggests that binding of ligands to BT1043 relies more upon interactions with the composite sugar residues than upon overall ligand conformation as previously observed for SusD. The diversity in amino acid sequence level likely reflects early divergence from a common ancestor, while the unique and conserved alpha-helical fold the SusD family suggests a similar function in glycan uptake.