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Mechanism of pathogen recognition by human dectin-2

Dectin-2, a C-type lectin on macrophages and other cells of the innate immune system, functions in response to pathogens, particularly fungi. The carbohydrate-recognition domain (CRD) in dectin-2 is linked to a transmembrane sequence that interacts with the common Fc receptor γ subunit to initiate i...

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Autores principales: Feinberg, Hadar, Jégouzo, Sabine A. F., Rex, Maximus J., Drickamer, Kurt, Weis, William I., Taylor, Maureen E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555199/
https://www.ncbi.nlm.nih.gov/pubmed/28652405
http://dx.doi.org/10.1074/jbc.M117.799080
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author Feinberg, Hadar
Jégouzo, Sabine A. F.
Rex, Maximus J.
Drickamer, Kurt
Weis, William I.
Taylor, Maureen E.
author_facet Feinberg, Hadar
Jégouzo, Sabine A. F.
Rex, Maximus J.
Drickamer, Kurt
Weis, William I.
Taylor, Maureen E.
author_sort Feinberg, Hadar
collection PubMed
description Dectin-2, a C-type lectin on macrophages and other cells of the innate immune system, functions in response to pathogens, particularly fungi. The carbohydrate-recognition domain (CRD) in dectin-2 is linked to a transmembrane sequence that interacts with the common Fc receptor γ subunit to initiate immune signaling. The molecular mechanism by which dectin-2 selectively binds to pathogens has been investigated by characterizing the CRD expressed in a bacterial system. Competition binding studies indicated that the CRD binds to monosaccharides with modest affinity and that affinity was greatly enhanced for mannose-linked α1–2 or α1–4 to a second mannose residue. Glycan array analysis confirmed selective binding of the CRD to glycans that contain Manα1–2Man epitopes. Crystals of the CRD in complex with a mammalian-type high-mannose Man(9)GlcNAc(2) oligosaccharide exhibited interaction with Manα1–2Man on two different termini of the glycan, with the reducing-end mannose residue ligated to Ca(2+) in a primary binding site and the nonreducing terminal mannose residue occupying an adjacent secondary site. Comparison of the binding sites in DC-SIGN and langerin, two other pathogen-binding receptors of the innate immune system, revealed why these two binding sites accommodate only terminal Manα1–2Man structures, whereas dectin-2 can bind Manα1–2Man in internal positions in mannans and other polysaccharides. The specificity and geometry of the dectin-2-binding site provide the molecular mechanism for binding of dectin-2 to fungal mannans and also to bacterial lipopolysaccharides, capsular polysaccharides, and lipoarabinomannans that contain the Manα1–2Man disaccharide unit.
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spelling pubmed-55551992017-08-16 Mechanism of pathogen recognition by human dectin-2 Feinberg, Hadar Jégouzo, Sabine A. F. Rex, Maximus J. Drickamer, Kurt Weis, William I. Taylor, Maureen E. J Biol Chem Glycobiology and Extracellular Matrices Dectin-2, a C-type lectin on macrophages and other cells of the innate immune system, functions in response to pathogens, particularly fungi. The carbohydrate-recognition domain (CRD) in dectin-2 is linked to a transmembrane sequence that interacts with the common Fc receptor γ subunit to initiate immune signaling. The molecular mechanism by which dectin-2 selectively binds to pathogens has been investigated by characterizing the CRD expressed in a bacterial system. Competition binding studies indicated that the CRD binds to monosaccharides with modest affinity and that affinity was greatly enhanced for mannose-linked α1–2 or α1–4 to a second mannose residue. Glycan array analysis confirmed selective binding of the CRD to glycans that contain Manα1–2Man epitopes. Crystals of the CRD in complex with a mammalian-type high-mannose Man(9)GlcNAc(2) oligosaccharide exhibited interaction with Manα1–2Man on two different termini of the glycan, with the reducing-end mannose residue ligated to Ca(2+) in a primary binding site and the nonreducing terminal mannose residue occupying an adjacent secondary site. Comparison of the binding sites in DC-SIGN and langerin, two other pathogen-binding receptors of the innate immune system, revealed why these two binding sites accommodate only terminal Manα1–2Man structures, whereas dectin-2 can bind Manα1–2Man in internal positions in mannans and other polysaccharides. The specificity and geometry of the dectin-2-binding site provide the molecular mechanism for binding of dectin-2 to fungal mannans and also to bacterial lipopolysaccharides, capsular polysaccharides, and lipoarabinomannans that contain the Manα1–2Man disaccharide unit. American Society for Biochemistry and Molecular Biology 2017-08-11 2017-06-26 /pmc/articles/PMC5555199/ /pubmed/28652405 http://dx.doi.org/10.1074/jbc.M117.799080 Text en © 2017 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle Glycobiology and Extracellular Matrices
Feinberg, Hadar
Jégouzo, Sabine A. F.
Rex, Maximus J.
Drickamer, Kurt
Weis, William I.
Taylor, Maureen E.
Mechanism of pathogen recognition by human dectin-2
title Mechanism of pathogen recognition by human dectin-2
title_full Mechanism of pathogen recognition by human dectin-2
title_fullStr Mechanism of pathogen recognition by human dectin-2
title_full_unstemmed Mechanism of pathogen recognition by human dectin-2
title_short Mechanism of pathogen recognition by human dectin-2
title_sort mechanism of pathogen recognition by human dectin-2
topic Glycobiology and Extracellular Matrices
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555199/
https://www.ncbi.nlm.nih.gov/pubmed/28652405
http://dx.doi.org/10.1074/jbc.M117.799080
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