Solution structure of a conformationally constrained Arg-Gly-Asp-like motif inserted into the alpha/beta scaffold of leiurotoxin I.
A monoclonal antibody, AC7, directed against the RGD-binding site of the GPIIIa subunit of the platelet fibrinogen receptor, interacts with activated platelet. The H3 region (H3, RQMIRGYFDV sequence) of the complementarity-determining region 3 heavy chain of AC7 inhibits platelet aggregation and fibrinogen binding to platelet. H3 contains the arginine, glycine and aspartate residues, but in an unusual order. The solution structure of the decapeptide has been studied by proton NMR. The NMR data suggested a helical equilibrium. To test whether the helical structure of H3 was biologically relevant, a conformationally constrained peptide with the RGD-like motif was designed. The sequence of a scorpion toxin (leiurotoxin I) has been modified in order to constrain the H3 sequence in a rigid helical conformation. The structure of leiurotoxin I consists of a beta-sheet and an alpha-helix, linked by three disulfide bridges. The structural feature of the chimeric peptide (H3-leiurotoxin) has been determined by standard two-dimensional NMR techniques. H3-Leiurotoxin structure closely resembles that of leiurotoxin I.
Kellenberger
E
E
Laboratoire de RMN, Supérieure de Biotechnologie de Strasbourg, France.
Mer
G
G
Kellenberger
C
C
Marguerie
G
G
Lefèvre
J F
JF
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012604:Scorpion Venoms / Q000138:chemical synthesis / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D012604:Scorpion Venoms; C056574:leiurotoxin I; C047981:arginyl-glycyl-aspartic acid