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Mapping molecular recognition of β1,3-1,4-glucans by a surface glycan-binding protein from the human gut symbiont Bacteroides ovatus

DOI: 10.1128/Spectrum.01826-21 DOI Help

Authors: Viviana Correia (NOVA University Lisbon) , Filipa Trovão (NOVA University Lisbon) , Benedita A. Pinheiro (NOVA University Lisbon) , Joana L. A. Bras (University of Lisbon) , Lisete M. Silva (Imperial College London) , Cláudia Nunes (University of Aveiro) , Manuel A. Coimbra (University of Aveiro) , Yan Liu (Imperial College London) , Ten Feizi (Imperial College London) , Carlos M. G. A. Fontes (University of Lisbon) , Barbara Mulloy (Imperial College London) , Wengang Chai (Imperial College London) , Ana Luisa Carvalho (University Lisbon) , Angelina S. Palma (NOVA University Lisbon)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Microbiology Spectrum

State: Published (Approved)
Published: November 2021
Diamond Proposal Number(s): 16609 , 24872

Open Access Open Access

Abstract: A multigene polysaccharide utilization locus (PUL) encoding enzymes and surface carbohydrate (glycan)-binding proteins (SGBPs) was recently identified in prominent members of Bacteroidetes in the human gut and characterized in Bacteroides ovatus. This PUL-encoded system specifically targets mixed-linkage β1,3-1,4-glucans, a group of diet-derived carbohydrates that promote a healthy microbiota and have potential as prebiotics. The BoSGBPMLG-A protein encoded by the BACOVA_2743 gene is a SusD-like protein that plays a key role in the PUL’s specificity and functionality. Here, we perform a detailed analysis of the molecular determinants underlying carbohydrate binding by BoSGBPMLG-A, combining carbohydrate microarray technology with quantitative affinity studies and a high-resolution X-ray crystallography structure of the complex of BoSGBPMLG-A with a β1,3-1,4-nonasaccharide. We demonstrate its unique binding specificity toward β1,3-1,4-gluco-oligosaccharides, with increasing binding affinities up to the octasaccharide and dependency on the number and position of β1,3 linkages. The interaction is defined by a 41-Å-long extended binding site that accommodates the oligosaccharide in a mode distinct from that of previously described bacterial β1,3-1,4-glucan-binding proteins. In addition to the shape complementarity mediated by CH-π interactions, a complex hydrogen bonding network complemented by a high number of key ordered water molecules establishes additional specific interactions with the oligosaccharide. These support the twisted conformation of the β-glucan backbone imposed by the β1,3 linkages and explain the dependency on the oligosaccharide chain length. We propose that the specificity of the PUL conferred by BoSGBPMLG-A to import long β1,3-1,4-glucan oligosaccharides to the bacterial periplasm allows Bacteroidetes to outcompete bacteria that lack this PUL for utilization of β1,3-1,4-glucans.

Diamond Keywords: Bacteria: Gut Microbiota

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Other Facilities: ESRF

Added On: 30/11/2021 09:17


Discipline Tags:

Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)