Invité Direction: Angelina Palma, GlycoLab, Lisbonne, Portugal – « Unraveling Glycan-Protein Interactions in Bacterial Systems: Integrating Glycan Microarrays with Structural Biology »

Résumé

Carbohydrate-binding modules (CBMs), SusD-like and surface-glycan-binding (SGBPs) proteins are key players in bacterial glycan recognition, enabling nutrient acquisition, bacterial colonization and adaptation to diverse ecological niches. This seminar will highlight how the integration of glycan microarrays with structural biology techniques, including X-ray crystallography, and bioinformatics is transforming our understanding of glycan-recognition by bacteria. Published and unpublished data will be presented for glycan-binding proteins (CBMs, SusD-like, SGBPs) from bacteria residing in different ecological niches, including Clostridium thermocellum in soil ecosystems, Ruminococcus flavefaciens in the rumen,focusing on their roles in binding to plant cell wall polysaccharides (e.g., cellulose, hemicellulose, pectin), and from Bacteroides, which specialize in capturing host-derived glycans, such as those from mucins. By integrating bioinformatics tools and databases—including CAZy for CBM classification, PULDB for polysaccharide utilization loci (PULs), UniProt for sequence annotations, and PDB for structural data—sequence-structure-function relationships that will dictate glycan-binding specificity are explored. Structural insights from X-ray crystallography coupled with high-throughput glycan microarray screening reveal the molecular mechanisms governing glycan recognition (1-6). This multidisciplinary approach bridges computational and experimental techniques, advancing the annotation, prediction, and engineering of glycan-binding proteins for applications in microbiome research, biotechnology, and glycan-based tools and therapeutics.

References:

1. Palma, A.S. et al. “Unravelling Glucan Recognition Systems by Glycome Microarrays Using the Designer Approach and Mass Spectrometry.” Molecular & Cellular Proteomics, 14, 2015, 974–88, doi:10.1074/mcp.M115.048272.

2. Ribeiro, D.O., et al. “Molecular Basis for the Preferential Recognition of Β1,3-1,4-Glucans by the Family 11 Carbohydrate-Binding Module from Clostridium Thermocellum.” FEBS Journal, 287:2723-2743, 2020.

3. Correia, Viviana G., et al. “Mapping Molecular Recognition of Β1,3-1,4-Glucans by a Surface Glycan-Binding Protein from the Human Gut Symbiont Bacteroides Ovatus.” Microbiology Spectrum, 22;9:e01826219, 2021.

4.  Li, C., Palma, A.S., et al. “Noncovalent microarrays from synthetic amino-terminating glycans: Implications in expanding glycan microarray diversity and platform comparison”. Glycobiology 31:931-946, 2021.

5.  Trovão, F., et al. “The structure of a Bacteroides thetaiotaomicron carbohydrate-binding module provides new insight into the recognition of complex pectic polysaccharides by the human microbiome”. J Struct Biol X, 7:100084, 2023.

6.  Ribeiro, D.O., et al. “CBMcarb-DB: Interface of the Three-Dimensional Landscape of Carbohydrate-Binding Modules.” in Carbohydrate Chemistry – Chemical and Biological Approaches, ed. A. Pilar Rauter. Y. Queneau, and A. S. Palma, Royal Society of Chemistry, vol. 46, 1-22, 2024.