Biological functions of fucose in mammals.
Michael Schneider,Esam Al-Shareffi,Esam Al-Shareffi,Robert S. Haltiwanger,Robert S. Haltiwanger +4 more
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TLDR
The known roles of fucose in mammalian physiology and pathophysiology are summarized and recent therapeutic advances for cancer and other diseases are discussed that are a direct result of improved understanding of the role that fucosylated proteins plays in these systems.Abstract:
Fucose is a 6-deoxy hexose in the l-configuration found in a large variety of different organisms. In mammals, fucose is incorporated into N-glycans, O-glycans and glycolipids by 13 fucosyltransferases, all of which utilize the nucleotide-charged form, GDP-fucose, to modify targets. Three of the fucosyltransferases, FUT8, FUT12/POFUT1 and FUT13/POFUT2, are essential for proper development in mice. Fucose modifications have also been implicated in many other biological functions including immunity and cancer. Congenital mutations of a Golgi apparatus localized GDP-fucose transporter causes leukocyte adhesion deficiency type II, which results in severe developmental and immune deficiencies, highlighting the important role fucose plays in these processes. Additionally, changes in levels of fucosylated proteins have proven as useful tools for determining cancer diagnosis and prognosis. Chemically modified fucose analogs can be used to alter many of these fucose dependent processes or as tools to better understand them. In this review, we summarize the known roles of fucose in mammalian physiology and pathophysiology. Additionally, we discuss recent therapeutic advances for cancer and other diseases that are a direct result of our improved understanding of the role that fucose plays in these systems.read more
Citations
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Small RNAs are modified with N-glycans and displayed on the surface of living cells.
Ryan A. Flynn,Kayvon Pedram,Stacy A. Malaker,Pedro J. Batista,Benjamin A. H. Smith,Alex G. Johnson,Benson M. George,Karim Majzoub,Peter W. Villalta,Jan E. Carette,Carolyn R. Bertozzi +10 more
TL;DR: Glycans modify lipids and proteins to mediate inter-and intramolecular interactions across all domains of life as mentioned in this paper, and RNA is used as a third scaffold for glycosylation.
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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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Protein O-fucosylation: structure and function.
TL;DR: The biological importance of these O-fucose glycans and molecular mechanisms by which they affect the function of the proteins they modify are described and predicted to influence secretion of targets including several extracellular proteases.
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The Functional Power of the Human Milk Proteome.
Junjie Zhu,Kelly A Dingess +1 more
TL;DR: This review will highlight each of the aforementioned components of human milk and emphasize the functionality of the proteome throughout lactation, including nutrient delivery and enhanced bioavailability of nutrients for growth, cognitive development, immune defense, and gut maturation.
References
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Unravelling the pathogenesis of inflammatory bowel disease
TL;DR: Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation as mentioned in this paper, which have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis.
Book
Essentials of Glycobiology
Ajit Varki,Richard D. Cummings,Jeffrey D. Esko,Hudson H. Freeze,Pamela Stanley,Carolyn R. Bertozzi,Gerald W. Hart,Marilynn E. Etzler +7 more
TL;DR: General principles - historical background and overview saccharide structure and nomenclature evolution of glycan diversity protein-glycan Interactions exploring the biological roles of glycans biosynthesis, metabolism, and function.
Journal ArticleDOI
Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular Toxicity
Robert L. Shields,Jadine Lai,Rodney G. Keck,Lori Y. O'Connell,Kyu Hong,Y. Gloria Meng,Stefanie Weikert,Leonard G. Presta +7 more
TL;DR: Antibody-dependent cellular cytot toxicity assays using purified peripheral blood monocytes or natural killer cells from several donors showed enhanced cytotoxicity, especially evident at lower antibody concentrations.
Journal ArticleDOI
The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity.
Toyohide Shinkawa,Kazuyasu Nakamura,Naoko Yamane,Emi Shoji-Hosaka,Yutaka Kanda,Mikiko Sakurada,Kazuhisa Uchida,Hideharu Anazawa,Mitsuo Satoh,Motoo Yamasaki,Nobuo Hanai,Kenya Shitara +11 more
TL;DR: The results indicate that the lack of fucosylation of IgG1 has the most critical role in enhancement of ADCC, although several reports have suggested the importance of Gal or bisecting GlcNAc and provide important information to produce the effective therapeutic antibody.
Journal ArticleDOI
Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura
Gallia Levy,William C. Nichols,Eric C.-Y. Lian,Tatiana Foroud,Jeanette N. McClintick,Beth McGee,Angela Y. Yang,David R. Siemieniak,Kenneth R. Stark,Ralph A. Gruppo,Ravindra Sarode,Susan B. Shurin,Visalam Chandrasekaran,Sally P. Stabler,Hernan Sabio,Eric E. Bouhassira,Jefferson D. Upshaw,David Ginsburg,Han-Mou Tsai +18 more
TL;DR: In this article, the ADAMTS family of zinc metalloproteinase genes (ADAMTS13) was identified as the molecular mechanism responsible for TTP, and it was shown that the deficiency of ADADTS13 is the molecular mechanisms responsible for the development of TTP.
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