Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Multiple glycosyltransferases are essential for the proper modification of alpha-dystroglycan, as mutations in the encoding genes cause congenital/limb-girdle muscular dystrophies. Here we elucidate further the structure of an O-mannose-initiated glycan on alpha-dystroglycan that is required to generate its extracellular matrix-binding polysaccharide. This functional glycan contains a novel ribitol structure that links a phosphotrisaccharide to xylose. ISPD is a CDP-ribitol (ribose) pyrophosphorylase that generates the reduced sugar nucleotide for the insertion of ribitol in a phosphodiester linkage to the glycoprotein. TMEM5 is a UDP-xylosyl transferase that elaborates the structure. We demonstrate in a zebrafish model as well as in a human patient that defects in TMEM5 result in muscular dystrophy in combination with abnormal brain development. Thus, we propose a novel structure-a ribitol in a phosphodiester linkage-for the moiety on which TMEM5, B4GAT1, and LARGE act to generate the functional receptor for ECM proteins having LG domains.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924997 | PMC |
| http://dx.doi.org/10.7554/eLife.14473 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chemical Synthesis of Oligosaccharides Derived from Serotype 35B and D Provides Molecular Insight in l-Ficolin Binding.
J Am Chem Soc
August 2025
Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht 3584 CG, the Netherlands.
The wide use of capsular polysaccharide (CPS) conjugate vaccines is causing serotype replacement, and the emergence of serotype 35B is concerning because of multidrug resistance. CPS of 35B is composed of pentasaccharide repeating units that are linked through phosphodiester linkages. One of the galactofuranose residues of the pentasaccharide is acetylated, which distinguishes it from invasive serotype 35D, lacking the acetyl ester.
View Article and Find Full Text PDFSubstrate flexibility of Mycoplasma fermentans mf1 phosphorylcholine transferase.
Glycoconj J
April 2025
Institute of Biochemistry, University of Natural Resources and Life Sciences, Muthgasse 18, Vienna, 1190, Austria.
Zwitterionic modifications of glycans such as phosphorylcholine or phosphoethanolamine occur in a wide range of prokaryotic and eukaryotic organisms and are known for interaction with the mammalian immune system. Unlike the biosynthesis of membrane phospholipids which is well elucidated, very little is known about the transfer of zwitterionic phosphodiester moieties onto glycoconjugates. The presence and function of relevant enzymes has been suggested by gene knockout or mutation and corresponding aberrant phosphorylcholine metabolism.
View Article and Find Full Text PDFSemisynthetic Glycoconjugates as Potential Vaccine Candidates Against Haemophilus influenzae Type a.
Chemistry
August 2024
Department of Chemistry, Università degli Studi di Milano, Milano, Italy.
Glycoconjugate vaccines are based on chemical conjugation of pathogen-associated carbohydrates with immunogenic carrier proteins and are considered a very cost-effective way to prevent infections. Most of the licensed glycoconjugate vaccines are composed of saccharide antigens extracted from bacterial sources. However, synthetic oligosaccharide antigens have become a promising alternative to natural polysaccharides with the advantage of being well-defined structures providing homogeneous conjugates.
View Article and Find Full Text PDFSynthesis and Preliminary Immunological Evaluation of a Pseudotetrasaccharide Related to a Repeating Unit of the Serotype 6A Capsular Polysaccharide.
Front Mol Biosci
December 2021
Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Article Synopsis
- A new compound called 2-aminoethyl glycoside of a specific pseudotetrasaccharide related to a bacterial capsular polysaccharide has been created.
- The synthesis involved preparing a protected pseudotrisaccharide and a 2-OH derivative, which were then connected through a phosphate bridge.
- Initial tests indicated that these compounds can trigger immune responses in mice and contain recognizable features by anti-serogroup 6 antibodies, suggesting potential applications in vaccines.
Structural features and immunological perception of the cell surface glycans of Lactobacillus plantarum: a novel rhamnose-rich polysaccharide and teichoic acids.
Carbohydr Polym
April 2020
Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy; Department of Agricultural Sciences, University of Naples, 80055 Portici, Italy. Electronic address:
The capsular material from Lactobacillus plantarum IMB19, an isolate from fermented vegetables, has been analyzed and our results demonstrate that most of the coat of this bacterium consists of glycerol- and ribitol-type teichoic acids, further decorated with other substituents (α-glucose and alanine), and of a capsular polysaccharide (CPS) with a linear nonasaccharide repeating unit, rich in rhamnose, interconnected to the next via a phosphodiester bridge. Stimulation of immune cells with the total capsular material resulted in the enhancement of immunostimulatory (IFNγ, TNF-α, IL-6 and IL-12) or immuno-regulatory (IL-10) cytokines in an in vitro splenocyte culture system. The capsular polysaccharide, and not the teichoic acids mixture, was responsible for the IFNγ production.
View Article and Find Full Text PDF