5VYB

Structure of the carbohydrate recognition domain of Dectin-2 complexed with a mammalian-type high mannose Man9GlcNAc2 oligosaccharide

Summary for 5VYB

• Entry DOI: 10.2210/pdb5vyb/pdb
• Descriptor: C-type lectin domain family 6 member A, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: carbohydrate-binding protein; lectin; glycoprotein, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 18313.18

Authors

Feinberg, H.,Jegouzo, S.A.F.,Rex, M.J.,Drickamer, K.,Taylor, M.E.,Weis, W.I. (deposition date: 2017-05-24, release date: 2017-07-05, Last modification date: 2024-11-20)

Primary citation

Feinberg, H.,Jegouzo, S.A.F.,Rex, M.J.,Drickamer, K.,Weis, W.I.,Taylor, M.E.
Mechanism of pathogen recognition by human dectin-2.
J. Biol. Chem., 292:13402-13414, 2017

PubMed 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 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 ManGlcNAc oligosaccharide exhibited interaction with Manα1-2Man on two different termini of the glycan, with the reducing-end mannose residue ligated to Ca 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.

PubMed: 28652405
DOI: 10.1074/jbc.M117.799080

Experimental method

X-RAY DIFFRACTION (2.4 Å)