The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin‐1

Manabe, Yoshiyuki; Marchetti, Roberta; Takakura, Yohei; Nagasaki, Masahiro; Nihei, Wataru; Takebe, Tomoyuki; Tanaka, Katsunori; Kabayama, Kazuya; Chiodo, Fabrizio; Hanashima, Shinya; Kamada, Y.; Miyoshi, Eiji; Dulal, Hari Prasad; Yamaguchi, Yoshiki; Adachi, Yoshiyuki; Ohno, Naohito; Tanaka, Hiroshi; Silipo, Alba; Fukase, Koichi; Molinaro, Antonio

doi:10.1002/ange.201911875

Cited by 7 publications

(7 citation statements)

References 40 publications

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“…This latter phenomenon has inspired the development of next-generation therapeutic monoclonal antibodies that more effectively engage FcgRIIIa and demonstrate superior antibody-dependent cellular cytotoxicity (ADCC) 11,12 . Recently, dectin-I was identified as the first endogenous lectin that specifically recognises core fucose 13 . Collectively, these and other findings demonstrate that FUT8 plays a central role in modulating the activity of many cell-surface receptors.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of substrate recognition and catalysis by fucosyltransferase 8

Järvå

Dramićanin

Lingford

et al. 2020

Journal of Biological Chemistry

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Fucosylation of the inner-most Nacetylglucosamine (GlcNAc) of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, the development of monoclonal antibody therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well characterized and provide a framework for understanding N-glycan maturation in the Golgi; however the structural basis for these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here, we describe several structures of mouse and human FUT8 in the apo state and in complex with guanosine diphosphate (GDP), a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolutions. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process. https://www.jbc.org/cgi/

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Section: Introductionmentioning

confidence: 99%

Structural basis of substrate recognition and catalysis by fucosyltransferase 8

Järvå

Dramićanin

Lingford

et al. 2020

Journal of Biological Chemistry

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“…Thus, it should be noted that the role of N-glycan modifications can be different between proteins. We reported that dectin-1 specifically recognized core fucosylated IgG and did not interact with other core fucosylated proteins, suggesting that core fucose on IgG has specific physiological functions [82]. The role of N-glycans on distinct proteins is an important topic for future work.…”

Section: Functional Analysis Of N-glycans On Glycoproteinsmentioning

confidence: 95%

“…STD-NMR using a fluorine derivative (2D STD-TOCSYreF) indicated that the mannose on the α1,3-branched chain was more strongly recognized by PSA than the mannose on the α1,6-branched chain [81]. In addition, dectin-1, which recognizes fungal β-glucan, was found to recognize core fucose on immunoglobulin (IgG) [82]. STD-NMR analysis indicated that dectin-1 interacted not only with core fucose but also with an Fmoc group attached to the amino group of asparagine introduced at the reducing end.…”

Section: Analysis Using Nmrmentioning

confidence: 99%

Recent Advances in the Chemical Biology of N-Glycans

2021

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Asparagine-linked N-glycans on proteins have diverse structures, and their functions vary according to their structures. In recent years, it has become possible to obtain high quantities of N-glycans via isolation and chemical/enzymatic/chemoenzymatic synthesis. This has allowed for progress in the elucidation of N-glycan functions at the molecular level. Interaction analyses with lectins by glycan arrays or nuclear magnetic resonance (NMR) using various N-glycans have revealed the molecular basis for the recognition of complex structures of N-glycans. Preparation of proteins modified with homogeneous N-glycans revealed the influence of N-glycan modifications on protein functions. Furthermore, N-glycans have potential applications in drug development. This review discusses recent advances in the chemical biology of N-glycans.

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“…Dectin-1, Man receptor, and DC-specific intercellular adhesion molecule 3 (ICAM3)-grabbing non-integrin (DC-SIGN) [ 20 ] can recognize Fuc in carbohydrate patterns, but their specificity differs. Dectin-1 is better known as a receptor for yeast β-glucans, zymosan, and laminarin [ 20 ], but it can recognize the core 1,6-Fuc on immunoglobulin G (IgG) in vitro [ 21 ]. The Man receptor has two separate C- and R-type lectin motifs: the first binds terminal Fuc, Man, or N -acetyl- D -glucosamine (GlcNAc); the second binds glycans with 3- or 4- O -sulfated N -acetylgalactosamine (GalNAc), or 3- O -sulfated Lewis x (Le x )/Le a [ 22 ].…”

Section: Recognition Of Bacterial Surface Antigensmentioning

confidence: 99%

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

Litvinova

Vakhitov

Skalinskaya

et al. 2021

IJMS

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The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed.

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The Core Fucose on an IgG Antibody is an Endogenous Ligand of Dectin‐1

Cited by 7 publications

References 40 publications

Structural basis of substrate recognition and catalysis by fucosyltransferase 8

Structural basis of substrate recognition and catalysis by fucosyltransferase 8

Recent Advances in the Chemical Biology of N-Glycans

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

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