Structural Basis of Ligand Selectivity by a Bacterial Adhesin Lectin Involved in Multispecies Biofilm Formation
| Autor: | Robert Eves, Hossein Zahiri, Jan-Hendrik Hehemann, Tyler D. R. Vance, Silvia Vidal-Melgosa, Corey A. Stevens, Peter L. Davies, Shuaiqi Guo |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Protein Conformation multispecies biofilms medicine.disease_cause Crystallography X-Ray Ligands Microbiology Fucose lectin-carbohydrate interactions 03 medical and health sciences chemistry.chemical_compound Virology Lectins medicine structural biology Adhesins Bacterial Marinomonas Binding selectivity 030304 developmental biology 0303 health sciences Binding Sites biology bacterial colonization and infection Ligand 030302 biochemistry & molecular biology Biofilm Lectin biochemical phenomena metabolism and nutrition QR1-502 3. Good health Bacterial adhesin chemistry Biochemistry Structural biology Vibrio cholerae Biofilms biology.protein repeats-in-toxin adhesins Research Article |
| Zdroj: | mBio mBio, Vol 12, Iss 2 (2021) |
| ISSN: | 2150-7511 |
| Popis: | Bacterial adhesins are key virulence factors that are essential for the pathogen-host interaction and biofilm formation that cause most infections. Many of the adhesin-driven cell-cell interactions are mediated by lectins. Carbohydrate recognition by lectins governs critical host-microbe interactions. MpPA14 (Marinomonas primoryensis PA14 domain) lectin is a domain of a 1.5-MDa adhesin responsible for a symbiotic bacterium-diatom interaction in Antarctica. Here, we show that MpPA14 binds various monosaccharides, with l-fucose and N-acetylglucosamine being the strongest ligands (dissociation constant [Kd], ∼150 μM). High-resolution structures of MpPA14 with 15 different sugars bound elucidated the molecular basis for the lectin’s apparent binding promiscuity but underlying selectivity. MpPA14 mediates strong Ca2+-dependent interactions with the 3,4-diols of l-fucopyranose and glucopyranoses, and it binds other sugars via their specific minor isomers. Thus, MpPA14 only binds polysaccharides like branched glucans and fucoidans with these free end groups. Consistent with our findings, adhesion of MpPA14 to diatom cells was selectively blocked by l-fucose, but not by N-acetyl galactosamine. The MpPA14 lectin homolog present in a Vibrio cholerae adhesin was produced and was shown to have the same sugar binding preferences as MpPA14. The pathogen’s lectin was unable to effectively bind the diatom in the presence of fucose, thus demonstrating the antiadhesion strategy of blocking infection via ligand-based antagonists. |
| Databáze: | OpenAIRE |
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