Recent advancements in understanding mammalian O-mannosylation.
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TLDR
This review will focus on recent discoveries delineating the various enzymes, structures and functions associated with O-mannose-initiated glycoproteins, and discusses the evolution of this pathway.Abstract:
The post-translational glycosylation of select proteins by O-linked mannose (O-mannose or O-man) is a conserved modification from yeast to humans and has been shown to be necessary for proper development and growth. The most well studied O-mannosylated mammalian protein is α-dystroglycan (α-DG). Hypoglycosylation of α-DG results in varying severities of congenital muscular dystrophies, cancer progression and metastasis, and inhibited entry and infection of certain arenaviruses. Defects in the gene products responsible for post-translational modification of α-DG, primarily glycosyltransferases, are the basis for these diseases. The multitude of clinical phenotypes resulting from defective O-mannosylation highlights the biomedical significance of this unique modification. Elucidation of the various O-mannose biosynthetic pathways is imperative to understanding a broad range of human diseases and for the development of novel therapeutics. In this review, we will focus on recent discoveries delineating the various enzymes, structures and functions associated with O-mannose-initiated glycoproteins. Additionally, we discuss current gaps in our knowledge of mammalian O-mannosylation, discuss the evolution of this pathway, and illustrate the utility and limitations of model systems to study functions of O-mannosylation.read more
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Global view of human protein glycosylation pathways and functions
TL;DR: This work predicts that use of (single-cell) transcriptomics, genetic screens, genetic engineering of cellular glycosylation capacities and custom design of glycoprotein therapeutics are advancements that will ignite wider integration of gly cosylation in general cell biology.
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Perspectives on Glycosylation and Its Congenital Disorders.
Bobby G. Ng,Hudson H. Freeze +1 more
TL;DR: This work highlights recent advancements that have resulted in a better understanding of human glycosylation disorders, perspectives for potential future therapies, and mysteries for which the authors continue to seek new insights and solutions.
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Congenital disorders of glycosylation.
TL;DR: Carohydrate deficient transferrin (CDT) and protein-linked glycan analysis with mass spectrometry can diagnose some subtypes of congenital disorders of glycosylation (CDG), while many currently rely on massively parallel genomic sequencing for diagnosis.
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Emerging structural insights into glycosyltransferase-mediated synthesis of glycans
TL;DR: Analysis of recent X-ray crystallography data on eukaryotic glycosyltransferases in complex with acceptor and donor substrates reveals structural features that govern substrate specificity and Glycosylation site selection.
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TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)-associated proteins.
TL;DR: This review presents an up‐to‐date summary of all the known disease‐related variations of genes encoding TRAPP‐associated proteins and the disorders linked to these variations which are now called TRAPPopathies.
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