Glycobiology articles within Nature Communications

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  • Article
    | Open Access

    Changes in glycoprotein expression are correlates of disease, but secreted glycoproteins cannot be accurately traced to their cell line of origin. Here, the authors develop a strategy to chemically tag and profile glycoproteins in a cell line-specific manner in co-culture systems and in vivo.

    • Anna Cioce
    • , Beatriz Calle
    •  & Benjamin Schumann

  • Article
    | Open Access

    Access to glycoenzymes for basic and applied research is limited by difficulties with their recombinant expression. Here, the authors describe a universal strategy for converting membrane-bound glycosyltransferases into water-soluble biocatalysts, which are expressed at high levels with retention of activity.

    • Thapakorn Jaroentomeechai
    • , Yong Hyun Kwon
    •  & Matthew P. DeLisa

  • Article
    | Open Access

    WbbB is a structurally unusual retaining glycosyltransferase. Here, the authors show that WbbB forms an Asp232-Kdo adduct prior to transfer to the saccharide acceptor. Therefore, unlike any previously studied glycosyltransferase, WbbB uses the double-displacement mechanism first proposed in 1953.

    • Taylor J. B. Forrester
    • , Olga G. Ovchinnikova
    •  & Matthew S. Kimber

  • Article
    | Open Access

    Here, Lopaticki et al. show that Plasmodium falciparum expresses a Dpy19 C-mannosyltransferase in the endoplasmic reticulum that glycosylates TSR domains. Functional characterization shows that PfDpy19 plays a critical role in transmission through mosquitoes as PfDpy19-deficiency abolishes C-glycosylation and destabilizes proteins relevant for gametogenesis and oocyst formation.

    • Sash Lopaticki
    • , Robyn McConville
    •  & Justin A. Boddey

  • Article
    | Open Access

    Matriglycan, a repeating disaccharide on α-dystroglycan, is the receptor for Lassa virus and specific extracellular matrix proteins. Here, the authors demonstrate that matriglycan, in a length-dependent tunable manner, is both necessary and sufficient for protein binding and viral infection.

    • M. Osman Sheikh
    • , Chantelle J. Capicciotti
    •  & Geert-Jan Boons

  • Article
    | Open Access

    Haloacid dehalogenase-like phosphatases are widespread across all domains of life and play a crucial role in the regulation of levels of sugar phosphate metabolites in cells. The authors report on the structure-guided engineering of phosphatases for dedicated substrate specificity for the conversion of sucrose and starch into fructose and mannose.

    • Chaoyu Tian
    • , Jiangang Yang
    •  & Yanhe Ma

  • Article
    | Open Access

    Mucin-domain glycoproteins are densely O-glycosylated proteins with unique secondary structure that imparts a large influence on cellular environments. Here, the authors develop a technique to selectively enrich and characterize mucin-domain glycoproteins from cell lysate and patient biofluids.

    • Stacy A. Malaker
    • , Nicholas M. Riley
    •  & Carolyn R. Bertozzi

  • Article
    | Open Access

    Glycogen is a major energy reserve in eukaryotes and is synthesised in part by glycogenin (GN) and glycogen synthase (GS). Here, authors describe the structural basis of GS regulation, specifically the mechanism of inactivation by phosphorylation.

    • Laura Marr
    • , Dipsikha Biswas
    •  & Elton Zeqiraj

  • Article
    | Open Access

    MUC1 is a heavily glycosylated protein on the cell surface. Here the authors show that MUC1 prefers negative over positive membrane curvature due to its bulky size, enabling MUC1 to avoid endocytosis and surface removal based on curvature preference.

    • Chih-Hao Lu
    • , Kayvon Pedram
    •  & Bianxiao Cui

  • Article
    | Open Access

    Leucyl-tRNA synthetase 1 (LARS1) is a leucine sensor for mTORC1 signaling and regulates leucine utilization depending on glucose availability. Here, the author show that O-GlcNAcylation of LARS1 is crucial for its ability to regulate mTORC1 activity and leucine metabolism upon glucose starvation.

    • Kibum Kim
    • , Hee Chan Yoo
    •  & Jung Min Han

  • Article
    | Open Access

    Streptococcal siglec-like binding regions (SLBRs) selectively bind cell surface glycans, but the basis for this selectivity is not understood. Here, the authors identify selectivity-modulating SLBR regions and study how changes in SLBR glycan selectivity affect interactions with human glycoprotein receptors.

    • Barbara A. Bensing
    • , Haley E. Stubbs
    •  & T. M. Iverson

  • Article
    | Open Access

    Cystinuria is caused by mutations in heterodimeric amino acid transporter known as system b0,+. Here, authors discover that Ca2+ stabilizes the interface between two system b0,+ regulatory subunits rBAT, leading to super-dimerization of the b0,+AT–rBAT heterodimer, facilitating system b0,+ maturation.

    • Yongchan Lee
    • , Pattama Wiriyasermkul
    •  & Shushi Nagamori

  • Article
    | Open Access

    The glycosyltransferase C1GalT1 directs a key step in protein O-glycosylation important for the expression of the cancer-associated Tn and T antigens. Here, the authors provide molecular insights into the function of C1GalT1 by solving the crystal structure of the Drosophila enzyme-substrate complex.

    • Andrés Manuel González-Ramírez
    • , Ana Sofia Grosso
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    Ribitol-phospate modification is essential for the function of α-dystroglycan, and mutations in ISPD, an enzyme that synthesizes the the ribitol-phosphate donor CDP-ribitol, cause muscular dystrophy. Here, the authors show that recovery of CDP-ribitol levels, either via AAV-mediated gene therapy or prodrug treatment, rescues dystroglycan function and pathology in a mouse model.

    • Hideki Tokuoka
    • , Rieko Imae
    •  & Tatsushi Toda

  • Article
    | Open Access

    EndoE is a multi-domain glycoside hydrolase of the human pathogen Enterococcus faecalis. Here, the authors present crystal structures of EndoE and provide biochemical insights into the molecular basis of EndoE’s substrate specificity and catalytic mechanism.

    • Mikel García-Alija
    • , Jonathan J. Du
    •  & Marcelo E. Guerin

  • Article
    | Open Access

    The colonic mucus layer is an organized system providing a physical barrier against pathogens and simultaneously harbouring the commensal flora. Here the authors report that transglutaminase 3 activity contributes to homeostasis of the colonic mucus layer and the lack of this enzymatic activity leads to increased susceptibility against DSS-induced colitis in mice.

    • Jack D. A. Sharpen
    • , Brendan Dolan
    •  & Christian V. Recktenwald

  • Article
    | Open Access

    Pseudomonas aeruginosa employs lectins to bind to its host cells, and is known to be the major cause of lung infections. Lectin B (LecB) from Pseudomonas aeruginosa binds specifically to galactose and fucose and is important for pathogenicity, adhesion and biofilm formation. In this work, the neutron crystal structure (1.9 Å) of the deuterated LecB/Ca/fucose complex is reported. The structure, in combination with perdeuteration of the ligand and the receptor allowed the observation of hydrogen atoms, protonation states and hydrogen bonds involved in the interaction between pathogenic bacteria and host cells. Thus the study provides structural insights into the mechanism of high affinity binding of LecB to its targets.

    • Lukas Gajdos
    • , Matthew P. Blakeley
    •  & Anne Imberty

  • Article
    | Open Access

    Steviol glycosides from the plant Stevia rebaudiana are already used as lowcalorie sweeteners, but the most abundant naturally occurring compounds have a bitter aftertaste. Here, the authors characterize and engineer rice glycosyltransferase OsUGT91C1 to facilitate the large-scale production of naturally rare but palatable glycosides Reb D and Reb M

    • Jinzhu Zhang
    • , Minghai Tang
    •  & Wei Cheng

  • Article
    | Open Access

    The modification of proteins with O-linked β-N-acetylglucosamine (OGlcNAc) plays roles in regulation of numerous cellular functions while incorrect O-GlcNAcylation patterns are linked to disease. Here, the authors report a cryo-EM structure of full-length O-GlcNAc transferase (OGT), the only enzyme responsible for O-GlcNAcylation.

    • Richard W. Meek
    • , James N. Blaza
    •  & Gideon J. Davies

  • Article
    | Open Access

    Mutations in genes critical for proper intra-Golgi transport can cause human syndromes due to defects in glycosylation of proteins. Here, the authors identify a human variant of Syntaxin-5 that causes fatal multisystem disease and mislocalization of glycosyltransferases due to altered Golgi transport.

    • Peter T. A. Linders
    • , Eveline C. F. Gerretsen
    •  & Geert van den Bogaart

  • 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

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