3SGE

Crystal structure of mAb 17.2 in complex with R13 peptide

Summary for 3SGE

• Entry DOI: 10.2210/pdb3sge/pdb
• Related: 3SGD
• Descriptor: Light Chain, Heavy Chain, R13 peptide, ... (5 entities in total)
• Functional Keywords: immunoglobulin, antigen binding, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 6
• Total formula weight: 98546.02

Authors

Pizarro, J.C.,Boulot, G.,Hontebeyrie, M.,Bentley, G.A. (deposition date: 2011-06-14, release date: 2011-11-09, Last modification date: 2024-11-27)

Primary citation

Pizarro, J.C.,Boulot, G.,Bentley, G.A.,Gomez, K.A.,Hoebeke, J.,Hontebeyrie, M.,Levin, M.J.,Smulski, C.R.
Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2 Beta protein: implications in cross-reactivity
Plos Negl Trop Dis, 5:e1375-e1375, 2011

PubMed Abstract: Patients with Chronic Chagas' Heart Disease possess high levels of antibodies against the carboxyl-terminal end of the ribosomal P2ß protein of Trypanosoma cruzi (TcP2ß). These antibodies, as well as the murine monoclonal antibody (mAb) 17.2, recognize the last 13 amino acids of TcP2ß (called the R13 epitope: EEEDDDMGFGLFD) and are able to cross-react with, and stimulate, the ß1 adrenergic receptor (ß1-AR). Indeed, the mAb 17.2 was able to specifically detect human β1-AR, stably transfected into HEK cells, by flow cytometry and to induce repolarisation abnormalities and first degree atrioventricular conduction block after passive transfer to naïve mice. To study the structural basis of this cross-reactivity, we determined the crystal structure of the Fab region of the mAb 17.2 alone at 2.31 Å resolution and in complex with the R13 peptide at 1.89 Å resolution. We identified as key contact residues on R13 peptide Glu3, Asp6 and Phe9 as was previously shown by alanine scanning. Additionally, we generated a model of human β1-AR to elucidate the interaction with anti-R13 antibodies. These data provide an understanding of the molecular basis of cross-reactive antibodies induced by chronic infection with Trypanosoma cruzi.

PubMed: 22069505
DOI: 10.1371/journal.pntd.0001375

Experimental method

X-RAY DIFFRACTION (1.89 Å)