Glycobiology

  • 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
  • Article
    | Open Access

    Proteoglycans are glycosylated proteins that play a number of structural and signalling functions. Here, Corti, Wang et al. show that the N-terminal sequence of proteoglycan Syndecan-2 selectively increases 6-O sulfation of its heparan sulfate chains, and that this promotes formation of a ternary Sdc2/VEGFA/VEGFR2 complex leading to increased angiogenesis.

    • Federico Corti
    • , Yingdi Wang
    •  & Michael Simons
  • Article
    | Open Access

    Mass spectrometry facilitates large-scale glycosylation profiling but in-depth analysis of intact glycopeptides is still challenging. Here, the authors show that activated ion electron transfer dissociation is suitable for glycopeptide fragmentation and improves glycoproteome coverage.

    • Nicholas M. Riley
    • , Alexander S. Hebert
    •  & Joshua J. Coon
  • Article
    | Open Access

    Proteins continuously undergo non-enzymatic modifications such as glycation, which accumulate under physiological conditions but can be enhanced in disease. Here the authors characterise histone glycation, provide evidence that it affects chromatin, particularly in breast cancer, and identify DJ-1 as a deglycase.

    • Qingfei Zheng
    • , Nathaniel D. Omans
    •  & Yael David
  • Article
    | Open Access

    The glycome of parasites can have immunomodulatory properties or help to avoid immune surveillance, but details are unknown. Here, Martini et al. characterize the N-glycome of the canine heartworm, reveal an unprecedented complexity, particularly in anionic N-glycans, and determine recognition by components of the immune system.

    • Francesca Martini
    • , Barbara Eckmair
    •  & Katharina Paschinger
  • Article
    | Open Access

    The promoter variant rs35705950 confers a gain of function to the MUC5B gene and is the dominant risk factor for idiopathic pulmonary fibrosis. Here the authors show that mice overexpressing Muc5b in distal airspaces show impaired mucociliary clearance and increased susceptibility to bleomycin-induced lung fibrosis, and that both characteristics are reduced by treatment with a mucolytic agent.

    • Laura A. Hancock
    • , Corinne E. Hennessy
    •  & David A. Schwartz
  • Article
    | Open Access

    Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

    • Min-Dian Li
    • , Nicholas B. Vera
    •  & Xiaoyong Yang
  • Article
    | Open Access

    The type III secretion system effectors NleB and SseK are glycosyltransferases (GT) that specifically glycosylate arginine residues. Here the authors provide insights into their mechanism by combining X-ray crystallography, NMR, enzyme kinetics measurements, molecular dynamics simulations and in vivo experiments and show that SseK/NleB enzymes are retaining GTs.

    • Jun Bae Park
    • , Young Hun Kim
    •  & Hyun-Soo Cho
  • Article
    | Open Access

    HIV envelope (Env) is a potential vaccine antigen and its N-glycans are part of the epitope of broadly neutralizing antibodies. Here, the authors show that glycosylation of Env from infectious virus closely matches Env from recombinant membrane-bound trimers, while it differs significantly from recombinant soluble, cleaved Env trimers.

    • Liwei Cao
    • , Matthias Pauthner
    •  & James C. Paulson
  • Article
    | Open Access

    The activity of glycosyltransferase GnT-V correlates with cancer malignancy and poor prognosis but its mechanism of action is poorly understood. Here, the authors solve crystal structures of free and substrate analog-bound GnT-V, providing insights into its catalytic mechanism and a basis for GnT-V inhibition.

    • Masamichi Nagae
    • , Yasuhiko Kizuka
    •  & Yoshiki Yamaguchi
  • Article
    | Open Access

    Aberrant glycosylation patterns on cancer cells promote several pro-tumorigenic functions, including enhancing tumor cell proliferation. Here the authors provide data that show melanoma cells downregulate GCNT2 with consequent loss of I-branched glycans; this leads to the formation of extended i-linear glycans and enhances melanoma growth via increases, in part, by IGF-1- and extracellular matrix-induced signaling.

    • Jenna Geddes Sweeney
    • , Jennifer Liang
    •  & Charles J. Dimitroff
  • Article
    | Open Access

    Several therapeutics are glycosylated proteins, yet the analysis of their specific glycosylation patterns remains challenging. Here the authors demonstrate an approach for the detailed characterization of glycosylated biopharmaceuticals applied to the determination of the glycoproteoform profile of glycoengineered variants of erythropoietin.

    • Tomislav Čaval
    • , Weihua Tian
    •  & Albert J. R. Heck
  • Article
    | Open Access

    Leukocytes are coated with glycans that modulate immune function through interactions with lectins. Here, the authors characterize the N-glycan repertoire of human tonsillar B cells. They report that Gal-9 is an intrinsic regulator of B cell activation that may differentially modulate BCR signaling at steady state and within germinal centers due to expression of I-branched glycans.

    • N. Giovannone
    • , J. Liang
    •  & C. J. Dimitroff
  • Article
    | Open Access

    The galectin family of secreted lectins are important regulators of immune cell function; however, their role in B cell responses is poorly understood. Here, the authors identify IgM-BCR as a ligand for galectin-9. In resting naive cells, they show that galectin-9 mediates a close association between IgM and CD22.

    • Anh Cao
    • , Nouf Alluqmani
    •  & Bebhinn Treanor
  • Article
    | Open Access

    Gram-positive bacterial envelopes comprise proteinaceous surface layers (S-layers) important for survival and virulence that are often anchored to the cell wall through secondary cell wall polymers. Here the authors use a structural and biophysical approach to define the molecular mechanism of this important interaction.

    • Ryan J. Blackler
    • , Arturo López-Guzmán
    •  & Stephen V. Evans
  • Article
    | Open Access

    The ability to produce homogeneous glycoproteins is expected to advance fundamental understanding in glycoscience, but current in vivo-based production systems have several limitations. Here, the authors develop an E. coli extract-based one-pot system for customized production of N-linked glycoproteins.

    • Thapakorn Jaroentomeechai
    • , Jessica C. Stark
    •  & Matthew P. DeLisa
  • Article
    | Open Access

    Endoglycosidase S only recognizes one particular type of glycan within IgG antibodies but the molecular basis for this high specificity is not fully understood. Here, the authors present the crystal structure of product-bound Endoglycosidase S, revealing the determinants for its glycan specificity.

    • Beatriz Trastoy
    • , Erik Klontz
    •  & Marcelo E. Guerin
  • Article
    | Open Access

    Sialic acid transporters (SiaT) are required for sialic acid uptake in a number of human pathogens and are of interest as targets for antimicrobial drug development. Here the authors present the substrate bound SiaT structure from the uropathogen Proteus mirabilis and provide insights into the mechanism of sialic acid transport.

    • Weixiao Y. Wahlgren
    • , Elin Dunevall
    •  & Rosmarie Friemann
  • Article
    | Open Access

    The specific glycosylation patterns of biological drugs often impact the efficacy and safety of the therapeutic product. Here the authors describe a native mass spectrometry approach that allows the resolution of highly complex glycosylation patterns on large proteins, which they apply to the therapeutic Fc-fusion protein Etanercept.

    • Therese Wohlschlager
    • , Kai Scheffler
    •  & Christian G. Huber
  • Article
    | Open Access

    Glycans, interaction platforms protruding from the surface of cells, are hard to study due to their diverse architecture. Here, the authors present a method to obtain cells carrying defined glycans, which can then be used to find proteins specifically recognizing these tags.

    • Jennie Grace Briard
    • , Hao Jiang
    •  & Peng Wu
  • Article
    | Open Access

    Mammalian GPI membrane anchors are modified by GalNAc to confer structural diversity but the biosynthetic pathway is poorly understood. Here, the authors identify and characterize the Golgi-resident GPI-GalNAc transferase PGAP4, providing insights into the initial step of GPI-GalNAc biosynthesis.

    • Tetsuya Hirata
    • , Sushil K. Mishra
    •  & Taroh Kinoshita
  • Article
    | Open Access

    The mucus layer is an important physical niche within the gut which harbours a distinct microbial community. Here the authors show that specific carbohydrate-binding modules associated with bacterial carbohydrate-active enzymes are mucus adhesins that target regions of the distal colon rich in sialomucins.

    • C. David Owen
    • , Louise E. Tailford
    •  & Nathalie Juge
  • Article
    | Open Access

    Teichoic acid is bound to peptidoglycan (wall teichoic acid, WTA) or to membrane glycolipids (lipoteichoic acid, LTA) in most Gram-positive bacteria. Here, the authors identify a putative ligase required for the assembly of LTA, but not WTA, and important for Streptococcus pneumoniae virulence in mouse models.

    • Nathalie Heß
    • , Franziska Waldow
    •  & Nicolas Gisch
  • Article
    | Open Access

    Wnt proteins mediate embryonic development but how protein localization and patterning is regulated is unclear. Here, the authors show that distinct structures with different heparan sulfate modifications (‘N-sulfo-rich’ and ‘N-acetyl-rich’) regulate cellular localization and signal transduction of Wnt8 in Xenopus.

    • Yusuke Mii
    • , Takayoshi Yamamoto
    •  & Masanori Taira
  • Article
    | Open Access

    GalNAc transferases’ (GalNAc-Ts) catalytic domains are connected to a lectin domain through a flexible linker. Here the authors present a structural analysis of GalNAc-T4 that implicates the linker region as modulator of the orientations of the lectin domain, which in turn imparts substrate specificity.

    • Matilde de las Rivas
    • , Erandi Lira-Navarrete
    •  & Ramon Hurtado-Guerrero
  • Article
    | Open Access

    Carrageenans, major cell wall polysaccharides of red macroalgae, are metabolised by marine heterotrophic bacteria through unclear mechanisms. Here, the authors identify an unusual polysaccharide-utilization locus encoding carrageenan catabolism in a marine bacterium, and characterise the complete pathway.

    • Elizabeth Ficko-Blean
    • , Aurélie Préchoux
    •  & Gurvan Michel
  • Article
    | Open Access

    IgG glycosylation is an important factor in immune function, yet the molecular details of protein glycosylation remain poorly understood. The data-driven approach presented here uses large-scale plasma IgG mass spectrometry measurements to infer new biochemical reactions in the glycosylation pathway.

    • Elisa Benedetti
    • , Maja Pučić-Baković
    •  & Jan Krumsiek
  • Article
    | Open Access

    Copper-dependent lytic polysaccharide monooxygenases (LPMOs) oxidatively cleave polysaccharides. Here the authors present a structure-function characterization of fungal LPMOs, showing that a particular LPMO cleaves xylan using a mechanism that involves an alternative copper coordination geometry.

    • T. J. Simmons
    • , K. E. H. Frandsen
    •  & P. Dupree
  • Article
    | Open Access

    O-linked β-N-acetyl glucosamine (O-GlcNAc) is an important protein modification that is hydrolyzed by O-GlcNAcase (OGA). Here the authors give insights into OGA substrate recognition by presenting four human OGA structures complexed with glycopeptide substrates containing a single O-GlcNAc modification on either a serine or threonine.

    • Baobin Li
    • , Hao Li
    •  & Jiaoyang Jiang
  • Article
    | Open Access

    PCSK9 interacts with LDL receptor, causing its degradation, and consequently reduces the clearance of LDL. Here, Gustafsen et al. show that PCSK9 interacts with heparan sulfate proteoglycans and this binding favors LDLR degradation. Pharmacological inhibition of this binding can be exploited as therapeutic intervention to lower LDL levels.

    • Camilla Gustafsen
    • , Ditte Olsen
    •  & Simon Glerup
  • Article
    | Open Access

    POGLUT1 is a protein-O-glucosyltransferase that transfers glucose and xylose to the EGF-like domains of Notch and other signaling receptors. Here the authors report the structure of human POGLUT1 in complexes with 3 different EGF-like domains and donor substrates and shed light on the enzyme’s substrate specificity and catalytic mechanism

    • Zhijie Li
    • , Michael Fischer
    •  & James M. Rini
  • Article
    | Open Access

    Protein glycosylation is an essential post-translational modification which analysis is complicated by the diversity of glycan composition and heterogeneity at individual attachment sites. Here the authors describe a method to selectively enrich N-linked glycopeptides to facilitate the detection of micro-heterogeneity in N-glycosylation.

    • Minyong Chen
    • , Xiaofeng Shi
    •  & James C. Samuelson
  • Article
    | Open Access

    Many biopharmaceuticals exhibit mixed heterogeneity in their post-translational modifications (PTMs) that are essential for their function. Here the authors use a combination of mass spectrometry techniques to analyse human erythropoietin (EPO) and properdin to discover new PTMs on properdin and derive a biosimilarity score for various sources of EPO.

    • Yang Yang
    • , Fan Liu
    •  & Albert J. R. Heck
  • Article
    | Open Access

    Immunologically-active glycans are promising vaccine candidates but can be difficult to synthesize. Here, the authors show that pentavalent display of a minimal disaccharde epitope on a chemical scaffold can mimic a native C. difficileglycan antigen, representing a simple approach to synthetic vaccine production.

    • Felix Broecker
    • , Jonas Hanske
    •  & Peter H. Seeberger