Topological analysis of the functional mimicry between a peptide and a carbohydrate moiety

被引:49
作者
Kaur, KJ [1 ]
Khurana, S [1 ]
Salunke, DM [1 ]
机构
[1] NATL INST IMMUNOL, STRUCT BIOL UNIT, NEW DELHI 110067, INDIA
关键词
D O I
10.1074/jbc.272.9.5539
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 off these analogs was found to have a direct correlation with the topological relationship between peptide and carbohydrate ligands.
引用
收藏
页码:5539 / 5543
页数:5
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