6XAQ

Alpha-methyl-glucose-bound structure of Marinomonas primoryensis PA14 carbohydrate-binding domain

Summary for 6XAQ

• Entry DOI: 10.2210/pdb6xaq/pdb
• Descriptor: Antifreeze protein, CALCIUM ION, methyl alpha-D-glucopyranoside, ... (4 entities in total)
• Functional Keywords: alpha-methyl-glucose-mppa14 complex, pa14 domain, carbohydrate-binding protein, sugar binding protein
• Biological source: Marinomonas primoryensis
• Total number of polymer chains: 1
• Total formula weight: 20693.21

Authors

Guo, S.,Davies, P.L. (deposition date: 2020-06-04, release date: 2021-06-02, Last modification date: 2023-10-18)

Primary citation

Guo, S.,Vance, T.D.R.,Zahiri, H.,Eves, R.,Stevens, C.,Hehemann, J.H.,Vidal-Melgosa, S.,Davies, P.L.
Structural Basis of Ligand Selectivity by a Bacterial Adhesin Lectin Involved in Multispecies Biofilm Formation.
Mbio, 12:-, 2021

PubMed Abstract: Carbohydrate recognition by lectins governs critical host-microbe interactions. PA14 ( 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 PA14 binds various monosaccharides, with l-fucose and -acetylglucosamine being the strongest ligands (dissociation constant [ ], ∼150 μM). High-resolution structures of PA14 with 15 different sugars bound elucidated the molecular basis for the lectin's apparent binding promiscuity but underlying selectivity. PA14 mediates strong Ca-dependent interactions with the 3,4-diols of l-fucopyranose and glucopyranoses, and it binds other sugars via their specific minor isomers. Thus, PA14 only binds polysaccharides like branched glucans and fucoidans with these free end groups. Consistent with our findings, adhesion of PA14 to diatom cells was selectively blocked by l-fucose, but not by -acetyl galactosamine. The PA14 lectin homolog present in a adhesin was produced and was shown to have the same sugar binding preferences as PA14. 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. 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. Our study reveals for the first time the molecular basis underlying the binding selectivity of a common bacterial adhesin lectin from the marine bacterium , homologs of which are found in both environmental and pathogenic species. The lectin-ligand interactions illustrated at the atomic level guided the identification of a ligand that serves as an inhibitor to block bacterium-host adhesion. With conventional bactericidal antibiotics losing their potency due to resistance, our work gives critical insight into an antiadhesion strategy to treat bacterial infections.

PubMed: 33824212
DOI: 10.1128/mBio.00130-21

Experimental method

X-RAY DIFFRACTION (1.2 Å)