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

Authors :
Annabelle Varrot
Anna Bernardi
Rafael Bermeo
Centre de Recherches sur les Macromolécules Végétales (CERMAV)
Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Dipartimento di Chimica [Milano, Italy]
Università degli studi di Milano [Milano]
Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Università degli Studi di Milano [Milano] (UNIMI)
Source :
Molecules, Molecules, MDPI, 2020, 25 (2), pp.248. ⟨10.3390/molecules25020248⟩, Molecules, Vol 25, Iss 2, p 248 (2020), Volume 25, Issue 2, 'Molecules ', vol: 25, pages: 248-1-248-15 (2020)
Publication Year :
2020
Publisher :
HAL CCSD, 2020.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Database :
OpenAIRE
Journal :
Molecules, Molecules, MDPI, 2020, 25 (2), pp.248. ⟨10.3390/molecules25020248⟩, Molecules, Vol 25, Iss 2, p 248 (2020), Volume 25, Issue 2, 'Molecules ', vol: 25, pages: 248-1-248-15 (2020)
Accession number :
edsair.doi.dedup.....9880cc272db88032db4ed1d3e8479bbe