Structural and functional consequences of peptide-carbohydrate mimicry - Crystal structure of a carbohydrate-mimicking peptide bound to concanavalin A

The functional consequences of peptide-carbohydrate mimicry were analyzed o n the basis of the crystal structure of concanavalin A (ConA) in complex wi th a carbohydrate-mimicking peptide, DVFYPYPYASGS, The peptide binds to the non-crystallographically related monomers of two independent dimers of Con A in two different modes, in slightly different conformations, demonstratin g structural adaptability in ConA-peptide recognition. In one mode, the pep tide has maximum interactions with ConA, and in the other, it shows relativ ely fewer contacts within this site but significant contacts with the symme try-related subunit, Neither of the peptide binding sites overlaps with the structurally characterized mannose and trimannose binding sites on Conk De spite this, the functional mimicry between the peptide and carbohydrate lig ands was evident. The peptide-inhibited ConA induced T cell proliferation i n a dose-dependent manner. The effect of the designed analogs of the peptid e on ConA-induced T cell proliferation and their recognition by the antibod y response against alpha-D-mannopyranoside indicate a role for aromatic res idues in functional mimicry. Although the functional mimicry was observed b etween the peptide and carbohydrate moieties, the crystal structure of the ConA-peptide complex revealed that the two peptide binding sites are indepe ndent of the methyl alpha-D-mannopyranoside binding site.