Topological analysis of the functional mimicry between a peptide and a carbohydrate moiety.
The shared surface topology of two chemically dissimilar but functionally equivalent molecular structures has been analyzed. A carbohydrate moiety (alpha-D-mannopyranoside) and a peptide molecule (DVFYPYPYASGS) bind to concanavalin A at a common binding site. The cross-reactivity of the polyclonal antibodies (pAbs) was used for understanding the topological relationship between these two independent ligands. The anti-alpha-D-mannopyranoside pAbs recognized various peptide ligands of concanavalin A, and the anti-DVFYPYPYASGS pAbs recognized the carbohydrate ligands, providing direct evidence of molecular mimicry. On the basis of differential binding of various rationally designed peptide analogs to the anti-alpha-D-mannopyranoside pAbs, it was possible to identify different peptide residues critical for the mimicry. The comparison of circular dichroism profiles of the designed analogs suggests that the carbohydrate mimicking conformation of the peptide ligand incorporates a polyproline type II structural fold. The concanavalin A binding activity of these analogs was found to have a direct correlation with the topological relationship between peptide and carbohydrate ligands.
Kaur
K J
KJ
Structural Biology Unit, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
Khurana
S
S
Salunke
D M
DM
D000818:Animals; D000906:Antibodies; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D003208:Concanavalin A / Q000378:metabolism; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000906:Antibodies; D009842:Oligopeptides; D010455:Peptides; C105091:aspartyl-valyl-phenylalanyl-tyrosyl-prolyl-tyrosyl-prolyl-tyrosyl-alanyl-seryl-glycyl-serine; D003208:Concanavalin A; D008358:Mannose