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Enzymatic conversion of human blood group A kidneys to universal blood group O
ABO blood group compatibility restrictions limit the availability of organs for patients awaiting transplantation. Here, the authors show the rapid enzymatic removal of blood group A antigens from the vasculature of human kidneys using normothermic and hypothermic machine perfusion technologies to make universal blood group O organs for transplantation.
- Serena MacMillan
- , Sarah A. Hosgood
- & Michael L. Nicholson
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| Open Access
Structure and function of Semaphorin-5A glycosaminoglycan interactions
Semaphorin 5A (Sema5A) forms complexes with heparan and chondroitin sulfate proteoglycans to regulate neuronal migration. Here, the authors show that the thrombospondin-like repeat 4 (TSR4) of Sema5A enables glycosaminoglycan association, multimerization, and neural progenitor cell distribution.
- Gergely N. Nagy
- , Xiao-Feng Zhao
- & E. Yvonne Jones
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| Open Access
Prediction of glycopeptide fragment mass spectra by deep learning
Deep learning has achieved a notable success in proteomics and is now emerging in glycoproteomics. Here, the authors develop a neural network-based method to predict mass spectra of intact glycopeptides and demonstrate its potential in data-dependent and data-independent acquisition glycoproteomics.
- Yi Yang
- & Qun Fang
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| Open Access
Lipoarabinomannan mediates localized cell wall integrity during division in mycobacteria
Mycobacteria have a unique cell envelope that includes characteristic lipoglycans, such as lipoarabinomannan. Here, Sparks et al. show that this lipoglycan plays roles in maintenance of local cell envelope integrity and septal placement during cell division.
- Ian L. Sparks
- , Takehiro Kado
- & Yasu S. Morita
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Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine
SenB is a Se-glycosyltransferase in the microbial biosynthesis pathway of selenoneine. Here, the authors perform the structure-function investigation, providing mechanistic insights into a two-step catalytic reaction of SenB.
- Wei Huang
- , Jun Song
- & Feng Long
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| Open Access
Molecular-level architecture of Chlamydomonas reinhardtii’s glycoprotein-rich cell wall
Chlamydomonas reinhardtii produces a glycoprotein-rich cell wall. Using nuclear magnetic resonance and mass spectrometry approaches, this study reveals unprecedented details on its protein and carbohydrate content, and provide an atomic-level architecture model.
- Alexandre Poulhazan
- , Alexandre A. Arnold
- & Isabelle Marcotte
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N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line
IgG molecules are glycosylated at a conserved asparagine residue of their constant region, and this modification is essential for the effector functions of their soluble form, such as complement activation and binding to Fcɣ receptors. Here authors show that in a model B-cell line, neither the expression nor the function of the membrane-bound form of IgG depend on glycosylation.
- Theresa Kissel
- , Veerle F. A. M. Derksen
- & René E. M. Toes
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Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum
The parasite Cryptosporidium has a reduced genome and is dependent on glycolysis for energy production. Here, Xu et al demonstrate that multiple pathways and glucose transporters exist in this organism which are essential for growth and facilitate energy acquisition and utilization.
- Rui Xu
- , Wandy L. Beatty
- & L. David Sibley
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MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation
B cell activation and differentiation entails metabolic remodelling, involving differential utilisation of monocarboxylates such as L-lactate and pyruvate. Here authors show by B-cell-specific genomic deletion of monocarboxylate transporter 1 (MCT1) that the consequential scarcity of pyruvate results in decreased acetylation of Histone H3 at K27, leading to decreased AID transcription and deficient class switching to IgG.
- Wenna Chi
- , Na Kang
- & Ligong Chen
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| Open Access
Selenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection
Metabolic oligosaccharide engineering (MOE) is a classical strategy for carbohydrate perception but suffers from glycan quantification. Here the authors develop a selenium-based metabolic oligosaccharide engineering strategy (SeMOE), based on elemental analysis, to quantitatively detect and visualize glycans both in vitro and in vivo.
- Xiao Tian
- , Lingna Zheng
- & Ran Xie
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Article
| Open Access
Site-selected in situ polymerization for living cell surface engineering
Constructing polymer-based mimics on the surface of cells has potential to manipulate cell behavior, but precise control of grafting sites is challenging. Here, the authors report a method for site selected radical polymerization on cell surfaces by metabolic labelling.
- Yihong Zhong
- , Lijia Xu
- & Huangxian Ju
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Article
| Open Access
Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection
Here authors generate a glycoengineered keratinocyte library delineating human glycosylation pathways. The use of this library reveals that each stage of the HSV-1 infectious cycle is sensitive to alterations in the cellular glycan landscape, identifying critical biosynthetic steps that could be exploited for targeting HSV-1.
- Ieva Bagdonaite
- , Irina N. Marinova
- & Hans H. Wandall
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| Open Access
Cryo-EM structure of human O-GlcNAcylation enzyme pair OGT-OGA complex
The single pair of enzymes in human, OGT and OGA, mediates protein OGlcNAcylation cycle. Here, authors provide cryo-EM structures of OGT-OGA complex, revealing how OGT selects native substrates and the mutual inhibition mechanism between OGT and OGA.
- Ping Lu
- , Yusong Liu
- & Haishan Gao
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O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations
The neurofilament cytoskeleton is critical for axon function and can be dysregulated in disease. Here, the authors show that intracellular glycosylation regulates a key neurofilament protein.
- Duc T. Huynh
- , Kalina N. Tsolova
- & Michael Boyce
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| Open Access
Molecular mechanism of decision-making in glycosaminoglycan biosynthesis
Heparan sulfate (HS) and chondroitin sulfate (CS) are different glycosaminoglycan chains that are attached to core proteins via the same linker tetrasaccharide, and it was unclear how core proteins are specifically modified with HS or CS. Here, the authors determine that the CS-initiating glycosyltransferase CSGALNACT2 is promiscuous, whereas the HS-initiating glycosyltransferase EXTL3 selects only certain core proteins for modification.
- Douglas Sammon
- , Anja Krueger
- & Erhard Hohenester
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| Open Access
Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE
Mucin glycoproteins are biologically relevant but are challenging to study. Here, the authors characterized the SmE enzyme and used it to glycoproteomic ally map immune checkpoint proteins. This information then drove MD simulations and binding assays to understand how glycosylation controls structure and function.
- Joann Chongsaritsinsuk
- , Alexandra D. Steigmeyer
- & Stacy A. Malaker
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| Open Access
Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines
Evolution of human H3N2 influenza has limited the specificity of hemagglutinin to a subset of glycan receptors, which brings challenges. By glyco-engineering cell lines, authors show the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for vaccines.
- Chika Kikuchi
- , Aristotelis Antonopoulos
- & James C. Paulson
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| Open Access
Identification and characterization of endo-α-, exo-α-, and exo-β-d-arabinofuranosidases degrading lipoarabinomannan and arabinogalactan of mycobacteria
Lipoarabinomannan and arabinogalactan in the mycobacterial cell wall contain d-arabinan core. Here, the authors identify and characterize the molecular structures and mechanisms of four bacterial enzymes that synergistically degrade the alpha- and beta-linkages of d-arabinan.
- Michiko Shimokawa
- , Akihiro Ishiwata
- & Kiyotaka Fujita
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| Open Access
Chemoenzymatic synthesis of genetically-encoded multivalent liquid N-glycan arrays
Cellular glycosylation is complex and heterogeneous, which is challenging to reproduce synthetically. Here, the authors report on enzymatic remodelling of multivalent glycosylated bacteriophages to produce genetically encoded library of N-glycans which can be used to measure glycan-protein interactions with lectins on the surface of live cells and organs.
- Chih-Lan Lin
- , Mirat Sojitra
- & Ratmir Derda
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| Open Access
Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine
Dendritic cell (DC) vaccines were among the first FDA-approved cancer immunotherapies but have been limited by the modest therapeutic efficacy. Here, authors report a facile metabolic glycan labeling approach to improving the cytotoxic T lymphocyte response and antitumor efficacy of DC vaccines.
- Joonsu Han
- , Rimsha Bhatta
- & Hua Wang
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| Open Access
The Gram-positive bacterium Romboutsia ilealis harbors a polysaccharide synthase that can produce (1,3;1,4)-β-d-glucans
(1,3;1,4)-β-d-Glucans are widely distributed in many organisms, but little is known about the enzymes responsible for their synthesis outside the grasses. Here, the authors report on the presence of (1,3;1,4)-β-d-glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis and identify and characterize the (1,3;1,4)-β-d-glucan synthase RiGT2.
- Shu-Chieh Chang
- , Mu-Rong Kao
- & Yves S. Y. Hsieh
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| Open Access
Glycopeptide database search and de novo sequencing with PEAKS GlycanFinder enable highly sensitive glycoproteomics
Accurate identification of intact glycopeptides from mass spectrometry data is essential for the characterization of glycosylation events in biological samples. Here, the authors propose GlycanFinder, a database search and de novo sequencing tool for the analysis of intact glycopeptides.
- Weiping Sun
- , Qianqiu Zhang
- & Baozhen Shan
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Article
| Open Access
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Siglec-15 inhibits T cell function in the tumor microenvironment. Here, the authors solve the crystal structure of antibody-bound Siglec-15, characterize its binding mode to sialic acids, and identify sialylated CD11b as one of its binding partners on T cells.
- Maria Pia Lenza
- , Leire Egia-Mendikute
- & June Ereño-Orbea
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| Open Access
Unraveling the glycosylated immunopeptidome with HLA-Glyco
Protein glycosylation plays a vital role in antigen recognition and immune modulation. Here, the authors present a computational workflow for identifying glycosylated peptides from mass spectrometry-based immunopeptidome data and investigate the properties of glycosylated MHC associated peptides.
- Georges Bedran
- , Daniel A. Polasky
- & Alexey I. Nesvizhskii
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| Open Access
The divisome but not the elongasome organizes capsule synthesis in Streptococcus pneumoniae
The bacterial cell envelope consists of multiple layers, the synthesis of which is coordinated through unclear mechanisms. Here, Nakamoto et al. reveal a mechanism linking the synthesis of capsular polysaccharides and cell wall peptidoglycan in pneumococci.
- Rei Nakamoto
- , Sarp Bamyaci
- & Lok-To Sham
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| Open Access
Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis
Spatial metabolomics are used to describe the location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice.
- Lindsey R. Conroy
- , Harrison A. Clarke
- & Ramon C. Sun
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| Open Access
Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket
Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer. Here, the authors combine a variety of chemical biology techniques to demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.
- Edward N. Schmidt
- , Dimitra Lamprinaki
- & Matthew S. Macauley
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| Open Access
Identification of d-arabinan-degrading enzymes in mycobacteria
Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, the authors identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria.
- Omar Al-Jourani
- , Samuel T. Benedict
- & Patrick J. Moynihan
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| Open Access
Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization
Bacteria often express multiple adhesive proteins (adhesins) for biofilm formation, but it is often unclear whether adhesins have specialized or redundant roles. Here, the authors show that Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces.
- Xin Huang
- , Thomas Nero
- & Jing Yan
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Article
| Open Access
A cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates
Here, the authors show that cell internalization of Engrailed2 not only relies on its homeodomain, but also involves a cationic region which interacts selectively with cell surface heparan sulfates.
- Sébastien Cardon
- , Yadira P. Hervis
- & Sandrine Sagan
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| Open Access
Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates
Here the authors present an HIV-1 vaccine strategy that combines Env stabilization, nanoparticle display, and glycan trimming, which improves neutralizing antibody responses, frequency of vaccine responders, and germinal center reactions in animal models.
- Yi-Nan Zhang
- , Jennifer Paynter
- & Jiang Zhu
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| Open Access
Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria
This study offers molecular insight into the sialidase and fucosidase decapping apparatus that initiates growth on mucin and promotes nutrient sharing by the dedicated mucolytic symbiont Akkermansia muciniphila with the mucus-associated microbiota.
- Bashar Shuoker
- , Michael J. Pichler
- & Maher Abou Hachem
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| Open Access
Turning universal O into rare Bombay type blood
People with the rare Bombay-type Oh blood group can only be transfused with Oh blood. Here, the authors characterize a bacterial α−1,2-fucosidase that can convert universal O type into rare Bombay type blood.
- Itxaso Anso
- , Andreas Naegeli
- & Marcelo E. Guerin
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Article
| Open Access
Identification of tagged glycans with a protein nanopore
The structural complexity of glycans seriously challenges the currently available analytical methods. Here, the authors report the identification of glycan isomers, glycans with varying chain lengths, and distinct branched glycans, via a glycan derivatization strategy and nanopore sensing.
- Minmin Li
- , Yuting Xiong
- & Guangyan Qing
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| Open Access
Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases
Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Here, the authors establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by the multi-modular enzymes EndoS and EndoS2
- Beatriz Trastoy
- , Jonathan J. Du
- & Marcelo E. Guerin
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| Open Access
Highly-sensitive label-free deep profiling of N-glycans released from biomedically-relevant samples
Glycans can serve as disease biomarkers. Here, the authors use label-free capillary electrophoresis-mass spectrometry for N-glycan profiling of minute sample amounts, resolving and characterizing previously undetected highly sialylated glycans and linkage isomers in a single analysis.
- Anne-Lise Marie
- , Somak Ray
- & Alexander R. Ivanov
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Article
| Open Access
Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence
Little is known about the role of glycolysis in cellular senescence. Here, authors report that glycolysis-derived serine biosynthesis activates PKM2 to phosphorylate histone H3T11, prevent cell senescence, and promote healthy aging.
- Yinsheng Wu
- , Lixu Tang
- & Xilan Yu
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Article
| Open Access
Identification of global inhibitors of cellular glycosylation
Here, the authors discover small molecules that inhibit glycosylation processes that occur in the Golgi apparatus of cells. The molecules reversibly inhibit formation of elaborate glycan structures without affecting secretion of glycoproteins.
- Daniel Madriz Sørensen
- , Christian Büll
- & Yoshiki Narimatsu
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| Open Access
Harnessing gut microbes for glycan detection and quantification
Detecting distinct glycans within heterogeneous mixtures is hindered by glycan structural complexity and diversity. Here the authors exploit the ability of gut microbes to sense different glycan structures in order to develop quantitative glycan biosensors by coupling bacterial detection machinery to an optimised luciferase reporter.
- Jennifer L. Modesto
- , Victoria H. Pearce
- & Guy E. Townsend II
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Article
| Open Access
Altered sulfation status of FAM20C-dependent chondroitin sulfate is associated with osteosclerotic bone dysplasia
Raine syndrome is associated with loss-of-function mutations of FAM20C. Here we show that Raine-originated mutations abrogate the interaction between FAM20C and C4ST-1 to alter chondroitin sulfate sulfation status and impact biomineralization in vitro and bone mineral density in vivo in mouse models, thereby serving clues for Raine syndrome etiology.
- Toshiyasu Koike
- , Tadahisa Mikami
- & Hiroshi Kitagawa
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Article
| Open Access
Peptidoglycan recycling mediated by an ABC transporter in the plant pathogen Agrobacterium tumefaciens
Some bacteria use the muropeptide transporter AmpG for uptake and recycling of cell wall fragments that are released during cell growth and division. Here, Gilmore & Cava show that the plant pathogen Agrobacterium tumefaciens, which lacks an AmpG homologue, uses a different type of transporter for the same function, which is essential for normal growth in this organism.
- Michael C. Gilmore
- & Felipe Cava
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Article
| Open Access
Intracellular galectin-3 is a lipopolysaccharide sensor that promotes glycolysis through mTORC1 activation
The carbohydrate binding protein galectin-3 has been linked to diabetes and cancer. Here, authors show that galectin-3 is a sensor of LPS, an important modulator of the mTORC1 signaling, and a critical regulator of glucose metabolism.
- Xing Chen
- , Chunyu Yu
- & Yongfeng Shang
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Article
| Open Access
pGlycoQuant with a deep residual network for quantitative glycoproteomics at intact glycopeptide level
Software tools for larger-scale intact glycopeptide quantification lag far behind, which hinders exploring the differential sitespecific glycosylation. Here, the authors report pGlycoQuant, a generic tool with a deep learning model for quantitative glycoproteomics at intact glycopeptide level.
- Siyuan Kong
- , Pengyun Gong
- & Weiqian Cao
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Article
| Open Access
Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors
Heparin is a family of complex carbohydrates binding to proteins to modulate cell activities. Here the authors report the synthesis, and conformations simulations of S-linked hemi-A heparosan [GlcA-S-GlcNAc]n, a thio-glycosidic uncleavable polysaccharide, and test it as human heparanase inhibitor.
- Peng He
- , Xing Zhang
- & Paul L. DeAngelis
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| Open Access
Molecular basis for glycan recognition and reaction priming of eukaryotic oligosaccharyltransferase
Oligosaccharyltransferase (OST), the central enzyme in N-glycosylation, modifies acceptor proteins by attaching a complex glycan. Cryo-EM structures of OST in distinct states, reveal the molecular basis of substrate recognition and catalysis.
- Ana S. Ramírez
- , Mario de Capitani
- & Kaspar P. Locher
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| Open Access
Structure of the human heparan sulfate polymerase complex EXT1-EXT2
Heparan sulfates are long and complex polysaccharides that mediate a large number of biological processes at the cell surface. Here, the authors provide structural and functional insights into the human EXT1-EXT2 complex that carries out the polymerization of heparan sulfate chains.
- Francisco Leisico
- , Juneina Omeiri
- & Rebekka Wild
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Article
| Open Access
Design and directed evolution of noncanonical β-stereoselective metalloglycosidases
Metallohydrolases are ubiquitous enzymes. Here the authors show the design and biochemical characterisation of metalloglycosidase by constructing a hydrolytically active Zn-binding site within a barrel-shaped outer membrane protein OmpF.
- Woo Jae Jeong
- & Woon Ju Song
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Article
| Open Access
Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection
Identification of host antiviral restriction factors could provide targets for antiviral therapy. Here, using a genome-wide CRISPR screen, the authors identify the glycosyltransferase B3GAT1 as a host protein which, when ectopically overexpressed, restricts influenza virus infection in vitro and in mice, as well as other viruses relying on sialic acid for entry.
- Joseph D. Trimarco
- , Sarah L. Nelson
- & Nicholas S. Heaton
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| Open Access
Cell-specific bioorthogonal tagging of glycoproteins
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
Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling