Glycobiology

  • Article
    | Open Access

    Here, Broszeit et al. show that circulating A/H3N2 viruses have evolved binding specificity to α2,6-sialosides on extended LacNAc moieties and therefore cannot agglutinate erythrocytes. Applying glycan remodeling allows to install functional receptors on erythrocytes and promotes identification of newly circulating variants to facilitate vaccine design.

    • Frederik Broszeit
    • , Rosanne J. van Beek
    •  & Geert-Jan Boons
  • Article
    | Open Access

    Glycomics can uncover important molecular changes but measured glycans are highly interconnected and incompatible with common statistical methods, introducing pitfalls during analysis. Here, the authors develop an approach to identify glycan dependencies across samples to facilitate comparative glycomics.

    • Bokan Bao
    • , Benjamin P. Kellman
    •  & Nathan E. Lewis
  • Article
    | Open Access

    Mucins play critical roles in maintaining the human microbiome, with their O-glycosylated tandem repeats (TRs) providing important cues for microbiota. Here, the authors develop a cellular platform for producing TRs with defined O-glycan structures to dissect the functions of TR O-glycosylation.

    • Rebecca Nason
    • , Christian Büll
    •  & Yoshiki Narimatsu
  • Article
    | Open Access

    Xyloglucans are polysaccharides found in plant cell walls. Here, the authors describe the xyloglucan depolymerization machinery of phytopathogenic Xanthomonas bacteria, and show that sugars released by this system induce the expression of key virulence factors driving pathogenesis.

    • Plinio S. Vieira
    • , Isabela M. Bonfim
    •  & Mario T. Murakami
  • Article
    | Open Access

    O-GalNAc glycans are essential in many biological and pathological processes, but difficult to access due to their structural complexity and synthetic challenges. Here, the authors report an efficient chemoenzymatic modular assembly strategy to construct structurally diverse O-GalNAc glycans, use the synthesised glycans to generate a synthetic mucin O-glycan microarray and profile binding specificities of glycan-binding proteins.

    • Shuaishuai Wang
    • , Congcong Chen
    •  & Lei Li
  • Article
    | Open Access

    Advanced glycation end-products (AGEs), such as methylglyoxal-derived hydroimidazolone isomer (MGH-1), are associated with disease and age-related disorders, and occur spontaneously, so it is unclear why specific protein sites become modified with specific AGEs. Here, the authors use a combinatorial peptide library to determine the chemical features that favour MGH-1 formation for short peptides and demonstrate a key role of tyrosine in this process.

    • Joseph M. McEwen
    • , Sasha Fraser
    •  & Rebecca A. Scheck
  • Article
    | Open Access

    The glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting enzyme in the hexosamine pathway producing uridine 5’-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), an essential glycosylation precursor. Here, the authors dissect the mechanisms of GFAT-1 regulation by protein kinase A (PKA)-mediated phosphorylation.

    • Sabine Ruegenberg
    • , Felix A. M. C. Mayr
    •  & Martin S. Denzel
  • Article
    | Open Access

    Alterations in glycosylation in tumours facilitate tumour progression. Here, the authors show that pancreatic ductal adenocarcinomas present increased sialylation, which stimulates the polarisation of monocytes via Siglec receptors, resulting in the generation of immune suppressive tumour associated macrophages.

    • Ernesto Rodriguez
    • , Kelly Boelaars
    •  & Yvette van Kooyk
  • Article
    | Open Access

    Glycolipids are glycoconjugates with important biological functions, but techniques for their analysis are deficient. Here, the authors report the use of cryogenic gas-phase infrared spectroscopy to investigate isomerism in a set of immunologically relevant glycolipids, and show that their structural features can be accurately resolved based on a narrow spectral fingerprint region.

    • Carla Kirschbaum
    • , Kim Greis
    •  & Kevin Pagel
  • Article
    | Open Access

    The fate of ocean carbon is determined by the balance between primary productivity and heterotrophic breakdown of that photosynthate. Here the authors show that diatoms produce a polysaccharide that resists bacterial degradation, accumulates, aggregates and stores carbon during spring blooms.

    • Silvia Vidal-Melgosa
    • , Andreas Sichert
    •  & Jan-Hendrik Hehemann
  • Article
    | Open Access

    Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins.

    • Yubo Liu
    • , Qiushi Chen
    •  & Jianing Zhang
  • Article
    | Open Access

    Comprehensive quantitative profiling of intact glycopeptides remains technically challenging. To address this, the authors here develop an integrated quantitative glycoproteomic workflow, including optimized sample preparation, multiplexed quantification and a dedicated data processing tool.

    • Pan Fang
    • , Yanlong Ji
    •  & Henning Urlaub
  • Article
    | Open Access

    C-glycosides are of pharmaceutical interest due to their stability against in vivo hydrolysis, however their enzymatic synthesis faces challenges. Here, the authors report a C-glycosyltransferase from Aloe barbadensis catalysing the C-glycosylation of drug-like acceptors to generate bioactive C-glycosides.

    • Kebo Xie
    • , Xiaolin Zhang
    •  & Jungui Dai
  • Article
    | Open Access

    Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunomodulatory receptors expressed on cells of the hematopoietic lineage. Here the authors demonstrate an approach for the identification of the glycan ligands of Siglecs, which is also applicable to other families of glycan-binding proteins.

    • Emily Rodrigues
    • , Jaesoo Jung
    •  & Matthew S. Macauley
  • Article
    | Open Access

    Thioglycoligases have proved useful for bonding carbohydrates to non-sugar acceptors, however, the scope of these biocatalysts is usually limited. Here, the authors engineer a xylosidase into a thioglycoligase with the ability to form O-, N-, S- and Se- glycosides together with sugar esters and phosphoesters.

    • Manuel Nieto-Domínguez
    • , Beatriz Fernández de Toro
    •  & María Jesús Martínez
  • Article
    | Open Access

    OgpA is an O-glycopeptidase from Akkermansia muciniphila, a mucin-degrading bacterium commonly found in the human gut. A thorough characterization of OgpA, including crystal structures in complex with substrate or product, reveals molecular basis of O-glycan recognition and enzyme specificity.

    • Beatriz Trastoy
    • , Andreas Naegeli
    •  & Marcelo E. Guerin
  • Article
    | Open Access

    Glycans are abundant biomolecules that mediate essential biological processes, but their chemical synthesis is challenging. Here, the authors report the synthesis of glycans up to a 128-mer, which represents the O-antigen of Bacteroides vulgatus lipopolysaccharide and one of the longest synthetic glycans to date.

    • Qian Zhu
    • , Zhengnan Shen
    •  & Biao Yu
  • Article
    | Open Access

    Epithelial cells that line the gut secrete complex glycoproteins that form a mucus layer to protect the gut wall from enteric pathogens. Here, the authors provide a comprehensive characterisation of endo-acting glycoside hydrolases expressed by mucin-degrading members of the microbiome that are able to cleave the O-glycan chains of a range of different animal and human mucins.

    • Lucy I. Crouch
    • , Marcelo V. Liberato
    •  & David N. Bolam
  • Article
    | Open Access

    Migration and homing of B cells to lymph nodes are important for B cell functions, but their regulation is poorly understood. Here, the authors show that B cell-specific deletion of Cosmc results in decreased protein O-glycosylation, loss of B cell homing to both lymphoid and nonlymphoid organs, and altered transendothelial migration implicated in this loss.

    • Junwei Zeng
    • , Mahmoud Eljalby
    •  & Richard D. Cummings
  • Article
    | Open Access

    Glycosylation plays a key role in shielding of immunogenic epitopes on viral spike (S) proteins. Here Watanabe et al. report that glycans of coronavirus SARS and MERS S proteins are heterogeneously distributed and do not form an efficacious high-density global shield which would ensure efficient immune evasion.

    • Yasunori Watanabe
    • , Zachary T. Berndsen
    •  & Max Crispin
  • Article
    | Open Access

    The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.

    • Natalie C. Bamford
    • , François Le Mauff
    •  & P. Lynne Howell
  • Article
    | Open Access

    Trefoil factors (TFFs) protect the mucosa and have various reported binding activities, but whether they share a common interaction mechanism has remained unclear. Here, the authors provide structural and biochemical evidence that all three human TFFs are divalent lectins that recognise the same disaccharide.

    • Michael A. Järvå
    • , James P. Lingford
    •  & Ethan D. Goddard-Borger
  • Article
    | Open Access

    Glycogen can be metabolized via glycogenolysis and the pentose phosphate pathway as well as into the production of UDP glucose, which when secreted can bind the P2Y14 receptor. Here the authors show how these glycogen metabolism pathways contribute to proinflammatory macrophage activation and susceptibility to sepsis.

    • Jingwei Ma
    • , Keke Wei
    •  & Bo Huang
  • Article
    | Open Access

    Heparan sulfates (HS) contain functionally relevant structural motifs, but determining their monosaccharide sequence remains challenging. Here, the authors develop an ion mobility mass spectrometry-based method that allows unambiguous characterization of HS sequences and structure-activity relationships.

    • Rebecca L. Miller
    • , Scott E. Guimond
    •  & Kevin Pagel
  • Article
    | Open Access

    Human gut bacteria depolymerize glycans into their sugar components, which otherwise cannot be processed by their host. Here, the authors characterise the endo-β-N-acetylglucosaminidase EndoBT-3987 from the Gram-negative symbiont Bacteroides thetaiotaomicron and present the crystal structures of ligand-free EndoBT-3987, a substrate bound complex and product complexes.

    • Beatriz Trastoy
    • , Jonathan J. Du
    •  & Marcelo E. Guerin
  • Article
    | Open Access

    Glycosylphosphatidylinositol (GPI) anchors are found on many cell surface proteins but their biosynthesis is not fully understood. Here, the authors identify genes involved in GPI galactosylation and reveal functional connections between GPI processing, glycosphingolipid biosynthesis and ER-associated degradation.

    • Yicheng Wang
    • , Yusuke Maeda
    •  & Taroh Kinoshita
  • Article
    | Open Access

    Glycosaminoglycans (GAGs) are an important nutrient source for the gut microbiome. Here, the authors characterize the genetic loci that underpins glycosaminoglycan utilization in Bacteroides thetaiotaomicron; providing insights into the metabolism of GAGs by a predominant member of the gut microbiota.

    • Didier Ndeh
    • , Arnaud Baslé
    •  & Alan Cartmell
  • Article
    | Open Access

    UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.

    • Holger Hengel
    • , Célia Bosso-Lefèvre
    •  & Bruno Reversade
  • Article
    | Open Access

    Post-translational modifications of phosphoglycerate kinase 1 (PGK1), a glycoytic enzyme, contribute to cancer progression. Here, the authors show that PGK1 is O-GlcNAcylated at T255, which induces its translocation into mitochondria to suppress the tricarboxylic acid cycle for colorectal cancer growth.

    • Hao Nie
    • , Haixing Ju
    •  & Wen Yi
  • Article
    | Open Access

    SPOR domains are present in bacterial proteins that recognize cell-wall peptidoglycan strands stripped of the peptide stems. Here, Alcorlo et al. show that, indeed, the presence of peptide stems abrogates binding to a SPOR domain, and provide insights into the molecular basis for recognition.

    • Martín Alcorlo
    • , David A. Dik
    •  & Juan A. Hermoso
  • Article
    | Open Access

    Constructing biosynthetic pathways to study and engineer glycoprotein structures is difficult. Here, the authors use GlycoPRIME, a cell-free workflow for mixing-and-matching glycosylation enzymes, to evaluate 37 putative glycosylation pathways and discover routes to 18 new glycoprotein structures

    • Weston Kightlinger
    • , Katherine E. Duncker
    •  & Michael C. Jewett
  • Article
    | Open Access

    Sialidases are glycoside hydrolases that cleave sialosides. Here the authors define the 3-D structure, alone and in complex with products and inhibitors, of the CAZy family GH156 sialidase, EnvSia156, showing it displays a catalytical (β/α) 8-barrel domain distinct from other sialidases and allowing description of its inverting catalytic mechanism.

    • Pedro Bule
    • , Léa Chuzel
    •  & Gideon J. Davies
  • Article
    | Open Access

    In-depth characterization of complex glycomes is complicated by the immense structural diversity of glycans. Here, the authors present a mass spectrometry-based strategy for untargeted, sensitive glycan profiling and identify 167 N-glycan compositions in total human plasma.

    • Guinevere S. M. Lageveen-Kammeijer
    • , Noortje de Haan
    •  & Manfred Wuhrer
  • Article
    | Open Access

    Bacteroidetes genomes contain polysaccharide utilization loci (PULs), each of which encodes enzymes for the breakdown of one particular glycan. By analyzing the enzyme composition of 13,537 PULs, the authors suggest that the natural glycan diversity is orders of magnitude lower than previously proposed.

    • Pascal Lapébie
    • , Vincent Lombard
    •  & Bernard Henrissat