Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungus Scedosporium apiospermum

Autor: Martínez-Alarcón, Dania, Balloy, Viviane, Bouchara, Jean-Philippe, Pieters, Roland, varrot, Annabelle
Přispěvatelé: Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Utrecht University [Utrecht], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Varrot, Annabelle
Rok vydání: 2020
Předmět:
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Science
Aspergillus fumigatus/metabolism
Oligosaccharides
Biochemistry
Article
Fungal Proteins
Binding Sites/physiology
Polysaccharides
Lectins
Humans
Polysaccharides/metabolism
Amino Acid Sequence
Scedosporium
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
General
[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Fungal Proteins/metabolism
[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Cells
Cultured
Fucose
Oligosaccharides/metabolism
Binding Sites
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Glycoconjugates/metabolism
Aspergillus fumigatus
Epithelial Cells
[SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Epithelial Cells/metabolism
Fucose/metabolism
Scedosporium/metabolism
Host-Pathogen Interactions/physiology
Host-Pathogen Interactions
Medicine
Lectins/metabolism
Structural biology
Glycoconjugates
Zdroj: 'Scientific Reports ', vol: 11, pages: 16109-1-16109-14 (2021)
Scientific Reports
Scientific Reports, Nature Publishing Group, 2021, 11, pp.16109. ⟨10.1038/s41598-021-95008-4⟩
Scientific Reports, 2021, 11, pp.16109. ⟨10.1038/s41598-021-95008-4⟩
Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
ISSN: 2045-2322
DOI: 10.1038/s41598-021-95008-4⟩
Popis: International audience; Scedosporium apiospermum is an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host–pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we present the first report on the identification and characterization of a lectin from S. apiospermum named SapL1. SapL1 was found using bioinformatics as a homolog to the conidial surface lectin FleA from Aspergillus fumigatus known to play a role in the adhesion to host glycoconjugates present in human lung epithelium. In our strategy to obtain recombinant SapL1, we discovered the importance of osmolytes to achieve its expression in soluble form in bacteria. Analysis of glycan arrays indicates specificity for fucosylated oligosaccharides as expected. Submicromolar affinity was measured for fucose using isothermal titration calorimetry. We solved SapL1 crystal structure in complex with α-methyl-L-fucoside and analyzed its structural basis for fucose binding. We finally demonstrated that SapL1 binds to bronchial epithelial cells in a fucose-dependent manner. The information gathered here will contribute to the design and development of glycodrugs targeting SapL1.
Databáze: OpenAIRE
Externí odkaz: