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Title: Mechanism of pathogen recognition by human dectin-2

Abstract

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 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-linked1-2 or1-4 to a second mannose residue. Glycan array analysis confirmed selective binding of the CRD to glycans that contain Man1-2Man epitopes. Crystals of the CRD in complex with a mammalian-type high-mannose Man9GlcNAc2 oligosaccharide exhibited interaction with Man1–2Man on two different termini of the glycan, with the reducing-end mannose residue ligated to Ca2 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 Man1-2Man structures, whereas dectin-2 can bind Man1–2Man in internal positions in mannans and other polysaccharides. The specificitymore » 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 Man1-2Man disaccharide unit.« less

Authors:
 [1];  [2];  [2];  [2];  [1];  [2]
  1. Stanford Univ., CA (United States). School of Medicine. Dept. of Structural Biology and and Molecular and Cellular Physiology
  2. Imperial College, London (United Kingdom). Dept. of Life Sciences
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
OSTI Identifier:
1625085
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Volume: 292; Journal Issue: 32; Journal ID: ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology

Citation Formats

Feinberg, Hadar, Jégouzo, Sabine A. F., Rex, Maximus J., Drickamer, Kurt, Weis, William I., and Taylor, Maureen E. Mechanism of pathogen recognition by human dectin-2. United States: N. p., 2017. Web. doi:10.1074/jbc.m117.799080.
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. United States. https://doi.org/10.1074/jbc.m117.799080
Feinberg, Hadar, Jégouzo, Sabine A. F., Rex, Maximus J., Drickamer, Kurt, Weis, William I., and Taylor, Maureen E. Mon . "Mechanism of pathogen recognition by human dectin-2". United States. https://doi.org/10.1074/jbc.m117.799080. https://www.osti.gov/servlets/purl/1625085.
@article{osti_1625085,
title = {Mechanism of pathogen recognition by human dectin-2},
author = {Feinberg, Hadar and Jégouzo, Sabine A. F. and Rex, Maximus J. and Drickamer, Kurt and Weis, William I. and Taylor, Maureen E.},
abstractNote = {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 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-linked1-2 or1-4 to a second mannose residue. Glycan array analysis confirmed selective binding of the CRD to glycans that contain Man1-2Man epitopes. Crystals of the CRD in complex with a mammalian-type high-mannose Man9GlcNAc2 oligosaccharide exhibited interaction with Man1–2Man on two different termini of the glycan, with the reducing-end mannose residue ligated to Ca2 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 Man1-2Man structures, whereas dectin-2 can bind Man1–2Man 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 Man1-2Man disaccharide unit.},
doi = {10.1074/jbc.m117.799080},
url = {https://www.osti.gov/biblio/1625085}, journal = {Journal of Biological Chemistry},
issn = {0021-9258},
number = 32,
volume = 292,
place = {United States},
year = {2017},
month = {6}
}

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    Works referencing / citing this record:

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    journal, February 2018


    N -Carboxyanhydride Polymerization of Glycopolypeptides That Activate Antigen-Presenting Cells through Dectin-1 and Dectin-2
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