High affinity sugar ligands of C-type lectin receptor langerin

Ota, Fumi; Hirayama, Tetsuya; Kizuka, Yasuhiko; Yamaguchi, Yoshiki; Fujinawa, Reiko; Nagata, Michio; Ismanto, Hendra S.; Lepenies, Bernd; Aretz, Jonas; Rademacher, Christoph; Seeberger, Peter H.; Angata, Takashi; Kitazume, Shinobu; Yoshida, Koichiro; Betsuyaku, Tomoko; Kida, Kenji; Yamasaki, Satoshi; Taniguchi, Naoyuki

doi:10.1016/j.bbagen.2018.04.004

Cited by 28 publications

(31 citation statements)

References 60 publications

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“…Considering its abundance in sulfation and positions of sulfate groups, KS can act as a versatile molecular switch for lectin affinity. Whereas galactose 6- O -sulfation masks disaccharide binding to galectin, this substitution provides for a high-affinity docking point for C-type lectin langerin 74 – 76 . Dynamic modulation of sulfation can thus contribute to make the KS platform a multi-purpose binding partner for tissue lectins 77 .…”

Section: Discussionmentioning

confidence: 99%

Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides

Miller

Cai

Wichapong

et al. 2020

Sci Rep

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Glycosaminoglycan chains of keratan sulfate proteoglycans appear to be physiologically significant by pairing with tissue lectins. Here, we used NMR spectroscopy and molecular dynamics (MD) simulations to characterize interactions of corneal keratan sulfate (KS), its desulfated form, as well as di-, tetra- (N-acetyllactosamine and lacto-N-tetraose) and octasaccharides with adhesion/growth-regulatory galectins, in particular galectin-3 (Gal-3). The KS contact region involves the lectin canonical binding site, with estimated KD values in the low µM range and stoichiometry of ~ 8 to ~ 20 galectin molecules binding per polysaccharide chain. Compared to Gal-3, the affinity to Gal-7 is relatively low, signaling preferences among galectins. The importance of the sulfate groups was delineated by using desulfated analogs that exhibit relatively reduced affinity. Binding studies with two related di- and tetrasaccharides revealed a similar decrease that underscores affinity enhancement by repetitive arrangement of disaccharide units. MD-based binding energies of KS oligosaccharide-loaded galectins support experimental data on Gal-3 and -7, and extend the scope of KS binding to Gal-1 and -9N. Overall, our results provide strong incentive to further probe the relevance of molecular recognition of KS by galectins in terms of physiological processes in situ, e.g. maintaining integrity of mucosal barriers, intermolecular (lattice-like) gluing within the extracellular meshwork or synaptogenesis.

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Section: Discussionmentioning

confidence: 99%

Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides

Miller

Cai

Wichapong

et al. 2020

Sci Rep

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“…Interestingly, the studies with sulfated LacNAc disaccharides have evidenced the existence of certain structural requirements underlying the stability of these interactions. [174,175] Thus, binding takes place when the 6S group is placed at the nonreducing Gal, whereas the presence of sulfate groups at the inner GlcNAc moiety seems to be irrelevant. Moreover, the interaction is abrogated after terminal sialylation (sulfated sialyl-LacNAc) or when the sulfate group is attached at position 3.…”

Section: Langerinmentioning

confidence: 99%

“…Otherwise, recently reported synthetic polymers capped with terminal 6S-LacNAc units have been shown to display very potent affinities (nM) and are able to exert anti-inflammatory activities in mouse models with chronic obstructive pulmonary disease (COPD). [175,179] These results certainly represent a new frontier in the treatment of COPD in cigarette smokers, as Langerhans cells have been reported to accumulate in broncoalveolar tissues of COPD patients. [180] As for other C-type lectins, the langerin-mediated recognition of Man-containing oligosaccharides has been exhaustively investigated from the structural perspective, especially using Xray crystallography.…”

Section: Langerinmentioning

confidence: 99%

Molecular Recognition in C‐Type Lectins: The Cases of DC‐SIGN, Langerin, MGL, and L‐Sectin

et al. 2020

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Carbohydrates play a pivotal role in intercellular communication processes. In particular, glycan antigens are key for sustaining homeostasis, helping leukocytes to distinguish damaged tissues and invading pathogens from healthy tissues. From a structural perspective, this cross-talk is fairly complex, and multiple membrane proteins guide these recognition processes, including lectins and Toll-like receptors. Since the beginning of this century, lectins have become potential targets for therapeutics for controlling and/or avoiding the progression of pathologies derived from an incorrect immune outcome, including infectious processes, cancer, or autoimmune diseases. Therefore, a detailed knowledge of these receptors is mandatory for the development of specific treatments. In this review, we summarize the current knowledge about four key C-type lectins whose importance has been steadily growing in recent years, focusing in particular on how glycan recognition takes place at the molecular level, but also looking at recent progresses in the quest for therapeutics.

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“…Nowadays, LC are considered to be a subset of tissue-resident macrophages that share key properties with macrophages such as embryonic origin and their capacity to self-renew within the epidermis (13, 14). LC are characterized by their expression of langerin (CD207), a C-type lectin receptor (CLR) required for antigen recognition and internalization that result in the formation of Birbeck granules (15). While LC capacity to cross-present antigens to CD8 + T cells remains a topic of debate (16–18), it is proven that LC ensure immune tolerance and protection in contact hypersensitivity (CHS) through the inhibition allergen-specific CD8 + T cells and the activation of specific regulatory T cells expressing the inducible T cell co-stimulator (ICOS) (19).…”

Section: Cutaneous Innate Immunitymentioning

confidence: 99%

Nrf2 Involvement in Chemical-Induced Skin Innate Immunity

et al. 2019

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Exposure to certain chemicals disturbs skin homeostasis. In particular, protein-reactive chemical contact sensitizers trigger an inflammatory immune response resulting in eczema and allergic contact dermatitis. Chemical sensitizers activate innate immune cells which orchestrate the skin immune response. This involves oxidative and inflammatory pathways. In parallel, the Nrf2/Keap1 pathway, a major ubiquitous regulator of cellular oxidative and electrophilic stress is activated in the different skin innate immune cells including epidermal Langerhans cells and dermal dendritic cells, but also in keratinocytes. In this context, Nrf2 shows a strong protective capacity through the downregulation of both the oxidative stress and inflammatory pathways. In this review we highlight the important role of Nrf2 in the control of the innate immune response of the skin to chemical sensitizers.

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High affinity sugar ligands of C-type lectin receptor langerin

Cited by 28 publications

References 60 publications

Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides

Structural insight into the binding of human galectins to corneal keratan sulfate, its desulfated form and related saccharides

Molecular Recognition in C‐Type Lectins: The Cases of DC‐SIGN, Langerin, MGL, and L‐Sectin

Nrf2 Involvement in Chemical-Induced Skin Innate Immunity

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