Featured
-
-
Article
| Open AccessMolecular 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
-
Article
| Open AccessHost heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation
The molecular mechanism of syncytium formation during SARS-CoV-2 infection is not fully understood. Zhang et al. now show that cell surface heparan sulfate enhances spike-induced ACE2 clustering and cell-cell fusion, which depends on a conserved ACE2 linker and is blocked by a heparan sulfate binding drug.
- Qi Zhang
- , Weichun Tang
- & Yihong Ye
-
Article
| Open AccessChemoenzymatic 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
-
Article
| Open AccessSiglec-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
-
Article
| Open AccessA Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection
Most conventional tuberculosis diagnostic tests rely on difficult to obtain sputum samples. In this proof-of-concept study, authors analyse whether pulmonary tuberculosis can be detected using exhaled breath condensate samples.
- Sergio Fabián Mosquera-Restrepo
- , Sophie Zuberogoïtia
- & Jérôme Nigou
-
Article
| Open AccessA universal glycoenzyme biosynthesis pipeline that enables efficient cell-free remodeling of glycans
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 AccessStructural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut
AM0627 is a bis-O-glycan mucinase that might work in the final steps of mucus degradation, thereby providing a carbon and nitrogen source for Akkermansia muciniphila. Here, the authors provide molecular insights into AM0627 function from X-ray crystallography and computer simulations.
- Víctor Taleb
- , Qinghua Liao
- & Ramon Hurtado-Guerrero
-
Article
| Open AccessGlycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses
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 AccessA versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands
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 AccessA stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A
The Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) is a component of commercial vaccines, but is unstable. Here, the authors generate glycomimetic oligomers that demonstrate higher stability than their natural counterparts and induce protective antibodies in mice.
- Jacopo Enotarpi
- , Marta Tontini
- & Roberto Adamo
-
Article
| Open AccessTrefoil factors share a lectin activity that defines their role in mucus
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 AccessStructural basis for substrate specificity and catalysis of α1,6-fucosyltransferase
Core-fucosylation of the N-glycan core is an essential biological modification and the α1,6- fucosyltransferase FUT8 is the only enzyme in humans that catalyses this modification through the addition of an α-1,6-linked fucose to N-glycans. Here the authors provide insights into FUT8 substrate recognition by determining the 1.95 Å crystal structure of human FUT8 complexed with GDP and a biantennary complex N-glycan.
- Ana García-García
- , Laura Ceballos-Laita
- & Ramon Hurtado-Guerrero
-
Article
| Open AccessHighly modified and immunoactive N-glycans of the canine heartworm
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 AccessDeciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens
Melioidosis and glanders are multifaceted infections caused by gram-negative bacteria. Here, the authors synthesize a series of oligosaccharides that mimic the lipopolysaccharides present on the pathogens’ surface and use them to develop novel glycoconjugates for vaccine development.
- Marielle Tamigney Kenfack
- , Marcelina Mazur
- & Charles Gauthier
-
Article
| Open Access[Au]/[Ag]-catalysed expedient synthesis of branched heneicosafuranosyl arabinogalactan motif of Mycobacterium tuberculosis cell wall
Arabinogalactan forms parts of the cellular envelope ofMycobacterium tuberculosis, however due to its size chemical synthesis is a massive task. Here the authors report the synthesis of branched heneicosafuranosyl arabinogalactan fragment by repeated use of a Au/Ag-catalysed glycosylation methodology.
- Shivaji A. Thadke
- , Bijoyananda Mishra
- & Srinivas Hotha
-
Article |
Glycopeptide analogues of PSGL-1 inhibit P-selectin in vitro and in vivo
Inhibiting the interaction between the membrane protein P-selectin and its ligand PSGL-1 is thought to block inflammation. Here the authors report an efficient stereoselective synthesis for PSGL-1 glycopeptide mimics and show that these compounds inhibit PSGL-1/P-selectin in vitro and in vivo.
- Venkata R. Krishnamurthy
- , Mohammed Y. R. Sardar
- & Elliot L. Chaikof