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bioRxiv · 10.1101/2020.11.18.389155

Structural basis of ligand selectivity by a bacterial adhesin lectin involved in multi- species biofilm formation

Guo, S.·Vance, T.·Zahiri, H.·Eves, R.·Stevens, C.·Hehemann, J.-H.·Vidal-Melgosa, S.·Davies, P.
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Abstract

Carbohydrate recognition by lectins governs critical host-microbe interactions. MpPA14 lectin is a domain of a 1.5-MDa adhesin responsible for a symbiotic bacterium-diatom interaction in Antarctica. Here we show MpPA14 binds various monosaccharides, with L-fucose and N-acetyl glucosamine being the strongest ligands (Kd ~ 150 M). High-resolution structures of MpPA14 with 15 different sugars bound elucidated the molecular basis for the lectins apparent binding promiscuity but underlying selectivity. MpPA14 mediates strong Ca2+-dependent interactions with the 3, 4 diols of L-fucopyranose and glucopyranoses, and 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. With MpPA14 lectin homologs present in adhesins of several pathogens, our work gives insight into an anti-adhesion strategy to block infection via ligand-based antagonists.

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Guo, S., Vance, T., Zahiri, H., Eves, R., Stevens, C., Hehemann, J.-H., Vidal-Melgosa, S., Davies, P.. 2020-11-18. Structural basis of ligand selectivity by a bacterial adhesin lectin involved in multi- species biofilm formation. https://doi.org/10.1101/2020.11.18.389155

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