Structural and Functional Consequences of Peptide-Carbohydrate Mimicry

Abstract

The functional consequences of peptide-carbohydrate mimicry were analyzed on the basis of the crystal structure of concanavalin A (ConA) in complex with a carbohydrate-mimicking peptide, DVFYPYPYASGS. The peptide binds to the non-crystallographically related monomers of two independent dimers of ConA in two different modes, in slightly different conformations, demonstrating structural adaptability in ConA-peptide recognition. In one mode, the peptide has maximum interactions with ConA, and in the other, it shows relatively fewer contacts within this site but significant contacts with the symmetry-related subunit. Neither of the peptide binding sites overlaps with the structurally characterized mannose and trimannose binding sites on ConA. Despite this, the functional mimicry between the peptide and carbohydrate ligands was evident. The peptide-inhibited ConA induced T cell proliferation in a dose-dependent manner. The effect of the designed analogs of the peptide on ConA-induced T cell proliferation and their recognition by the antibody response against ␣-D-mannopyranoside indicate a role for aromatic residues in functional mimicry. Although the functional mimicry was observed between the peptide and carbohydrate moieties, the crystal structure of the ConA-peptide complex revealed that the two peptide binding sites are independent of the methyl ␣-D-mannopyranoside binding site.

Functional Equality in the Absence of Structural Similarity

“…The binding of H 2 TPPS to ConA resembles that of the monosaccharide by virtue of it being able to mimic the interactions of the sugar with the help of bound water molecules. This is contrary to the sugar-mimicking peptides, which bind to ConA mimicking the hydropathy features of the carbohydrate ligands (11)(12). The symmetrical nature and multivalency of porphyrin leads to end-to-end cross-linking akin to that observed in cell-cell agglutination by ConA.…”

“…In addition to the carbohydrate ligands, ConA was also shown to bind a number of peptides sharing a common sequence motif Tyr-Pro-Tyr derived from phage display library (15,16). These peptides exhibit structural as well as functional mimicry of sugars but were found to bind at a site adjacent to the well characterized monosaccharide-binding site on ConA (10,11). The conserved Tyr-Pro-Tyr region of the peptides shares excellent similarity with the trimannose moiety in terms of structural superimposition and their surface hydrophobicity profiles.…”

High Resolution Crystal Structures of Siglec-7

“…Although the interactions with the symmetry-related loop are not extensive, this is one of the few examples of a peptide occupying a carbohydrate-binding pocket (30) and perhaps represents a first step toward a peptide-based Siglec-7 inhibitor. Interesting examples of a such peptide inhibitors have been described recently for family 18 chitinases (31) and concanavalin A (32).…”

Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome

“…Furthermore, strips were treated with periodate (100 m M sodium periodate in 100 m M sodium acetate, pH 5), which oxidises protein-glycan bonds [25]. The efficacy of periodate oxidation was tested by ConA staining.…”