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Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B
Clostridium difficile toxins are the primary causative agents for hospital-acquired diarrhea and pseudomembranous colitis. Numerous monoclonal antibodies (mAbs) targeting different domains of Clostridium difficile toxin have been reported. Here we report the crystal structures of two mAbs, B1 and B2...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034018/ https://www.ncbi.nlm.nih.gov/pubmed/35469152 http://dx.doi.org/10.1016/j.crstbi.2022.03.003 |
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author | Liu, Jinyu Kothe, Michael Zhang, Jianxin Oloo, Eliud Stegalkina, Svetlana Mundle, Sophia T. Li, Lu Zhang, Jinrong Cole, Leah E. Barone, Lucianna Biemann, Hans-Peter Kleanthous, Harry Anosova, Natalie G. Anderson, Stephen F. |
author_facet | Liu, Jinyu Kothe, Michael Zhang, Jianxin Oloo, Eliud Stegalkina, Svetlana Mundle, Sophia T. Li, Lu Zhang, Jinrong Cole, Leah E. Barone, Lucianna Biemann, Hans-Peter Kleanthous, Harry Anosova, Natalie G. Anderson, Stephen F. |
author_sort | Liu, Jinyu |
collection | PubMed |
description | Clostridium difficile toxins are the primary causative agents for hospital-acquired diarrhea and pseudomembranous colitis. Numerous monoclonal antibodies (mAbs) targeting different domains of Clostridium difficile toxin have been reported. Here we report the crystal structures of two mAbs, B1 and B2, in complex with the glycosyltransferase domain (GTD) of the Clostridium difficile toxin B (TcdB). B2 bound to the N-terminal 4 helix bundle of the GTD, a conserved membrane localization domain (MLD) found in the large clostridial glycosylating toxin family implicated in targeting plasma membrane. B1 bound to a distinct epitope at the hinge region between the MLD and the catalytic subdomain of the GTD. Functional studies revealed the potency of these mAbs in vitro and in vivo to be synergistic when given in combination. |
format | Online Article Text |
id | pubmed-9034018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-90340182022-04-24 Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B Liu, Jinyu Kothe, Michael Zhang, Jianxin Oloo, Eliud Stegalkina, Svetlana Mundle, Sophia T. Li, Lu Zhang, Jinrong Cole, Leah E. Barone, Lucianna Biemann, Hans-Peter Kleanthous, Harry Anosova, Natalie G. Anderson, Stephen F. Curr Res Struct Biol Research Article Clostridium difficile toxins are the primary causative agents for hospital-acquired diarrhea and pseudomembranous colitis. Numerous monoclonal antibodies (mAbs) targeting different domains of Clostridium difficile toxin have been reported. Here we report the crystal structures of two mAbs, B1 and B2, in complex with the glycosyltransferase domain (GTD) of the Clostridium difficile toxin B (TcdB). B2 bound to the N-terminal 4 helix bundle of the GTD, a conserved membrane localization domain (MLD) found in the large clostridial glycosylating toxin family implicated in targeting plasma membrane. B1 bound to a distinct epitope at the hinge region between the MLD and the catalytic subdomain of the GTD. Functional studies revealed the potency of these mAbs in vitro and in vivo to be synergistic when given in combination. Elsevier 2022-04-07 /pmc/articles/PMC9034018/ /pubmed/35469152 http://dx.doi.org/10.1016/j.crstbi.2022.03.003 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Liu, Jinyu Kothe, Michael Zhang, Jianxin Oloo, Eliud Stegalkina, Svetlana Mundle, Sophia T. Li, Lu Zhang, Jinrong Cole, Leah E. Barone, Lucianna Biemann, Hans-Peter Kleanthous, Harry Anosova, Natalie G. Anderson, Stephen F. Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B |
title | Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B |
title_full | Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B |
title_fullStr | Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B |
title_full_unstemmed | Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B |
title_short | Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B |
title_sort | novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of clostridium difficile toxin b |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034018/ https://www.ncbi.nlm.nih.gov/pubmed/35469152 http://dx.doi.org/10.1016/j.crstbi.2022.03.003 |
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