Imperial College London
Alternate

DrMaureenTaylor

Faculty of Natural Sciences, Department of Life Sciences

Reader in Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5281m.taylor

 
 
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Location

 

607Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Feinberg:2017:10.1074/jbc.M117.799080,
author = {Feinberg, H and Jégouzo, SAF and Rex, MJ and Drickamer, K and Weis, WI and Taylor, ME},
doi = {10.1074/jbc.M117.799080},
journal = {Journal of Biological Chemistry},
pages = {13402--13414},
title = {Mechanism of pathogen recognition by human dectin-2},
url = {http://dx.doi.org/10.1074/jbc.M117.799080},
volume = {292},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Dectin-2, a C-type lectin on macrophages and other cells of the innate immune system, functions in responses to pathogens, particularly fungi. The carbohydrate-recognition domain (CRD) in dectin-2 is linked to a transmembrane sequence that interacts with the common FcRγ 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 is 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 Man9GlcNAc2 oligosaccharide exhibited interaction with Manα1-2Man 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 Manα1-2Man structures, while 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.
AU  - Feinberg,H
AU  - Jégouzo,SAF
AU  - Rex,MJ
AU  - Drickamer,K
AU  - Weis,WI
AU  - Taylor,ME
DO  - 10.1074/jbc.M117.799080
EP  - 13414
PY  - 2017///
SN  - 1083-351X
SP  - 13402
TI  - Mechanism of pathogen recognition by human dectin-2
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M117.799080
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28652405
UR  - https://www.sciencedirect.com/science/article/pii/S0021925820385653?via%3Dihub
UR  - http://hdl.handle.net/10044/1/50262
VL  - 292
ER  -
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