title: The inhibition of the interaction between the anthrax toxin and its cellular receptor by an anti-receptor monoclonal antibody.
abstract: The high affinity binding of the anthrax protective antigen (PA) to one of its receptors, capillary morphogenesis protein 2 (CMG2), is essential for the intoxication process of anthrax toxin. To acquire novel research tools to study the PA-CMG2 interaction, we generated several anti-CMG2 monoclonal antibodies (MAbs). We demonstrated that one of the MAbs, 4B5, could inhibit PA-CMG2 binding and could also protect the sensitive cells against an anthrax lethal toxin challenge. We identified the epitope recognized by 4B5 and confirmed that the key residues of the epitope were the residues (119)YI-LK(125) of CMG2. Based on our results, we propose that 4B5 binds to the E122 pocket of CMG2 and interrupts the interaction between the pocket and the PA 2beta3-2beta4 loop. To our knowledge, this is the first report to illustrate that an anti-CMG2 antibody could inhibit the PA-CMG2 interaction and therefore interfere with the intoxication of anthrax toxin.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Guanlin
authors.initials: G
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Qu
authors.forename: Chenguang
authors.initials: C
authors.lastname: Cai
authors.forename: Yirong
authors.initials: Y
authors.lastname: Kong
authors.forename: Shuling
authors.initials: S
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D017433:Protein Structure, Secondary; D018000:Receptors, Peptide
chemical_list: C447150:ANTXR2 protein, human; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D000939:Epitopes; D008565:Membrane Proteins; D018000:Receptors, Peptide; C030325:anthrax toxin