Molecular Mimicry between a Monoclonal Antibody and One Subunit of Crotoxin, a Heterodimeric Phospholipase A2 Neurotoxin
-
V. Choumet
, P. Lafaye , C. Demangel , C. Bon and J.-C. Mazié
Abstract
Crotoxin is a heterodimeric phospholipase A2 neurotoxin formed by the non-covalent association of an acidic and non-toxic subunit, CA, and a basic and weakly toxic phospholipase A2, CB. The two subunits behave in a synergistic manner. CA enhances the lethal potency of CB by increasing its selectivity of action. The mAb A-56.36, directed against the non-toxic subunit CA, was previously shown to neutralize crotoxin toxicity by dissociating the crotoxin complex. In the present report, a polypeptide sequence similarity was observed between some CDRs of mAb A-56.36 and two regions of CB (pos. 60–80 and 95–110). Phage displayed peptides corresponding to VH2 and VH3 of mAb A-56.36 and to their homologous sequences in CB bind CA to different extents. This observation shows that mAb A-56.36 interacts with a region of CA involved in its interaction with CB, therefore mimicking the binding of CB to CA. A similar approach was used to determine the regions of ammodytoxin A and of agkistrodotoxin, two phospholipase A2 neurotoxins similar to CB, which are involved in the formation of heterocomplexes with CA. The analysis of these data contributes to the determination of stretches of amino acids which could constitute the paratope of mAb A-56.36, as well as the region of association of CB with CA in crotoxin.
Copyright ©1999 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Biosynthesis of Glycosylphosphatidylinositols in Mammals and Unicellular Microbes
- Activation of DNA Replication in Yeast by Recruitment of the RNA Polymerase II Transcription Complex
- On the Role of Symmetrical and Asymmetrical Chaperonin Complexes in Assisted Protein Folding
- Regulation of Cathepsin B Activity by Cysteine and Related Thiols
- Epitope Mapping of the Monoclonal Antibody MM12.10 to External MDR1 P-Glycoprotein Domain by Synthetic Peptide Scanning and Phage Display Technologies
- Molecular Mimicry between a Monoclonal Antibody and One Subunit of Crotoxin, a Heterodimeric Phospholipase A2 Neurotoxin
- Enzyme-Linked Immunosorbent Assay for the Measurement of JNK Activity in Cell Extracts
- Mitochondrial DNA Acts as Potential Promoter of the Baculovirus RNA Polymerase
- In Vitro Phosphorylation of Purified Glycosylphos-phatidylinositol-Specific Phospholipase D
- Cathepsin S and Cruzipain Are Inhibited by Equistatin from Actinia equina
- Lipopeptides as Dimerization Inhibitors of HIV-1 Protease
Articles in the same Issue
- Biosynthesis of Glycosylphosphatidylinositols in Mammals and Unicellular Microbes
- Activation of DNA Replication in Yeast by Recruitment of the RNA Polymerase II Transcription Complex
- On the Role of Symmetrical and Asymmetrical Chaperonin Complexes in Assisted Protein Folding
- Regulation of Cathepsin B Activity by Cysteine and Related Thiols
- Epitope Mapping of the Monoclonal Antibody MM12.10 to External MDR1 P-Glycoprotein Domain by Synthetic Peptide Scanning and Phage Display Technologies
- Molecular Mimicry between a Monoclonal Antibody and One Subunit of Crotoxin, a Heterodimeric Phospholipase A2 Neurotoxin
- Enzyme-Linked Immunosorbent Assay for the Measurement of JNK Activity in Cell Extracts
- Mitochondrial DNA Acts as Potential Promoter of the Baculovirus RNA Polymerase
- In Vitro Phosphorylation of Purified Glycosylphos-phatidylinositol-Specific Phospholipase D
- Cathepsin S and Cruzipain Are Inhibited by Equistatin from Actinia equina
- Lipopeptides as Dimerization Inhibitors of HIV-1 Protease