Cargando…

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cell...

Descripción completa

Detalles Bibliográficos
Autores principales: Bermeo, Rafael, Bernardi, Anna, Varrot, Annabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024360/
https://www.ncbi.nlm.nih.gov/pubmed/31936166
http://dx.doi.org/10.3390/molecules25020248
_version_ 1783498417525227520
author Bermeo, Rafael
Bernardi, Anna
Varrot, Annabelle
author_facet Bermeo, Rafael
Bernardi, Anna
Varrot, Annabelle
author_sort Bermeo, Rafael
collection PubMed
description Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.
format Online
Article
Text
id pubmed-7024360
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70243602020-03-11 BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information Bermeo, Rafael Bernardi, Anna Varrot, Annabelle Molecules Article Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties. MDPI 2020-01-07 /pmc/articles/PMC7024360/ /pubmed/31936166 http://dx.doi.org/10.3390/molecules25020248 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bermeo, Rafael
Bernardi, Anna
Varrot, Annabelle
BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
title BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
title_full BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
title_fullStr BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
title_full_unstemmed BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
title_short BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
title_sort bc2l-c n-terminal lectin domain complexed with histo blood group oligosaccharides provides new structural information
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024360/
https://www.ncbi.nlm.nih.gov/pubmed/31936166
http://dx.doi.org/10.3390/molecules25020248
work_keys_str_mv AT bermeorafael bc2lcnterminallectindomaincomplexedwithhistobloodgroupoligosaccharidesprovidesnewstructuralinformation
AT bernardianna bc2lcnterminallectindomaincomplexedwithhistobloodgroupoligosaccharidesprovidesnewstructuralinformation
AT varrotannabelle bc2lcnterminallectindomaincomplexedwithhistobloodgroupoligosaccharidesprovidesnewstructuralinformation