Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity.
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 t...
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ftdoajarticles:oai:doaj.org/article:6e608724de6844cdae7c66dd5579fbb0 2023-05-15T15:07:09+02:00 Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. Juan Carlos Pizarro Ginette Boulot Graham A Bentley Karina A Gómez Johan Hoebeke Mireille Hontebeyrie Mariano J Levin Cristian R Smulski 2011-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001375 https://doaj.org/article/6e608724de6844cdae7c66dd5579fbb0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3206007?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001375 https://doaj.org/article/6e608724de6844cdae7c66dd5579fbb0 PLoS Neglected Tropical Diseases, Vol 5, Iss 11, p e1375 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001375 2022-12-31T15:04:34Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 11 e1375 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Juan Carlos Pizarro Ginette Boulot Graham A Bentley Karina A Gómez Johan Hoebeke Mireille Hontebeyrie Mariano J Levin Cristian R Smulski Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Juan Carlos Pizarro Ginette Boulot Graham A Bentley Karina A Gómez Johan Hoebeke Mireille Hontebeyrie Mariano J Levin Cristian R Smulski |
author_facet |
Juan Carlos Pizarro Ginette Boulot Graham A Bentley Karina A Gómez Johan Hoebeke Mireille Hontebeyrie Mariano J Levin Cristian R Smulski |
author_sort |
Juan Carlos Pizarro |
title |
Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. |
title_short |
Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. |
title_full |
Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. |
title_fullStr |
Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. |
title_full_unstemmed |
Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2β protein: implications in cross-reactivity. |
title_sort |
crystal structure of the complex mab 17.2 and the c-terminal region of trypanosoma cruzi p2β protein: implications in cross-reactivity. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001375 https://doaj.org/article/6e608724de6844cdae7c66dd5579fbb0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 11, p e1375 (2011) |
op_relation |
http://europepmc.org/articles/PMC3206007?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001375 https://doaj.org/article/6e608724de6844cdae7c66dd5579fbb0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001375 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
11 |
container_start_page |
e1375 |
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1766338716317515776 |