Simple and practical sialoglycan encoding system reveals vast diversity in nature and identifies a universal sialoglycan-recognizing probe derived from AB 5 toxin B subunits
Simple and practical sialoglycan encoding system reveals vast diversity in nature and identifies a universal sialoglycan-recognizing probe derived from AB 5 toxin B subunits
Abstract Vertebrate sialic acids (Sias) display much diversity in modifications, linkages and underlying glycans. Slide microarrays allow high-throughput explorations of sialoglycan-protein interactions. A microarray presenting ～150 structurally-defined sialyltrisaccharides with various Sias linkages and modifications still poses challenges in planning, data sorting, visualization and analysis. To address these issues, we devised a simple 9-digit code for sialyltrisaccharides with terminal Sias and underlying two monosaccharides assigned from the non-reducing end, with three digits assigning a monosaccharide, its modifications, and linkage. Calculations based on the encoding system reveals >113,000 likely linear sialyltrisaccharides in nature. Notably a biantennary N-glycan with two terminal sialyltrisaccharides could thus have >1010 potential combinations and a triantennary N-glycan with three terminal sequences, >1015 potential combinations. While all possibilities likely do not exist in nature, sialoglycans encode enormous diversity. While glycomic approaches are used to probe such diverse sialomes, naturally-occurring bacterial AB5 toxin B subunits are simpler tools to track the dynamic sialome in biological systems. Sialoglycan microarray was utilized to compare sialoglycan-recognizing bacterial toxin B subunits. Unlike the poor correlation between B subunits and species phylogeny, there is stronger correlation with Sia-epitope preferences. Further supporting this pattern, we report a B subunit (YenB) from Yersinia enterocolitica (broad host range) recognizing almost all sialoglycans in the microarray, including 4-O-acetylated-Sias not recognized by a Y. pestis orthologue (YpeB). Differential Sia-binding patterns were also observed with phylogenetically-related B subunits from Escherichia coli (SubB), Salmonella Typhi (PltB), S. Typhimurium (ArtB), extra-intestinal E.coli (EcPltB), Vibrio cholera (CtxB), and cholera family homologue of E. coli (EcxB).
Verhagen Andrea、Diaz Sandra、Bruntse Anders Bech、Lewis Nathan E.、Paton Adrienne W.、Sasmal Aniruddha、Khedri Zahra、Srivastava Saurabh、Paton James C.、Chen Xi、Yu Hai、Beddoe Travis、Varki Ajit、Khan Naazneen、Kellman Benjamin P.、Varki Nissi
Glycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of CaliforniaGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of CaliforniaDepartment of Pediatrics, University of CaliforniaGlycobiology Research and Training Center, University of California||Department of Pediatrics, University of CaliforniaResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of AdelaideGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of CaliforniaGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of CaliforniaGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of CaliforniaResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of AdelaideDepartment of Chemistry, University of CaliforniaDepartment of Chemistry, University of CaliforniaDepartment of Animal, Plant and Soil Science and Centre for AgriBioscience, La Trobe UniversityGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of California||Department of Medicine, University of CaliforniaGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of CaliforniaDepartment of Pediatrics, University of CaliforniaGlycobiology Research and Training Center, University of California||Department of Cellular & Molecular Medicine, University of California
生物科学研究方法、生物科学研究技术分子生物学微生物学
Sialic acidglycobiologyN-acetylneuraminic acidN-glycolylneuraminic acidglycan microarrayglycan codesYersinia enterocoliticabacterial AB5 toxinB subunitglycan binding
Verhagen Andrea,Diaz Sandra,Bruntse Anders Bech,Lewis Nathan E.,Paton Adrienne W.,Sasmal Aniruddha,Khedri Zahra,Srivastava Saurabh,Paton James C.,Chen Xi,Yu Hai,Beddoe Travis,Varki Ajit,Khan Naazneen,Kellman Benjamin P.,Varki Nissi.Simple and practical sialoglycan encoding system reveals vast diversity in nature and identifies a universal sialoglycan-recognizing probe derived from AB 5 toxin B subunits[EB/OL].(2025-03-28)[2025-05-08].https://www.biorxiv.org/content/10.1101/2021.05.28.446191.点此复制
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