PDBsum entry 2it6

Immune system

PDB id: 2it6

Contents

Protein chain

132 a.a. *

Ligands

MAN-MAN

Metals

_CA ×3

Waters ×135

* Residue conservation analysis

PDB id:

2it6

Name:

Immune system

Title:

Crystal structure of dcsign-crd with man2

Structure:

Cd209 antigen. Chain: a. Synonym: dendritic cell-specific icam-3-grabbing nonintegrin 1, dc- sign1, dc-sign, c-type lectin domain family 4 member l. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cd209, clec4l. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.95Å R-factor: 0.196 R-free: 0.241

Authors:

W.I.Weis,H.Feinberg,R.Castelli,K.Drickamer,P.H.Seeberger

Key ref:

H.Feinberg et al. (2007). Multiple modes of binding enhance the affinity of DC-SIGN for high mannose N-linked glycans found on viral glycoproteins. J Biol Chem, 282, 4202-4209. PubMed id: 17150970 DOI: 10.1074/jbc.M609689200

Date:

19-Oct-06 Release date: 05-Dec-06

Protein chain

Q9NNX6  (CD209_HUMAN) -  CD209 antigen from Homo sapiens

Seq: 404 a.a.

Struc: 132 a.a.

DOI no: 10.1074/jbc.M609689200

J Biol Chem 282:4202-4209 (2007)

PubMed id: 17150970

Multiple modes of binding enhance the affinity of DC-SIGN for high mannose N-linked glycans found on viral glycoproteins.

H.Feinberg, R.Castelli, K.Drickamer, P.H.Seeberger, W.I.Weis.

ABSTRACT

The dendritic cell surface receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR specifically recognize high mannose N-linked carbohydrates on viral pathogens. Previous studies have shown that these receptors bind the outer trimannose branch Manalpha1-3[Manalpha1-6]Manalpha present in high mannose structures. Although the trimannoside binds to DC-SIGN or DC-SIGNR more strongly than mannose, additional affinity enhancements are observed in the presence of one or more Manalpha1-2Manalpha moieties on the nonreducing termini of oligomannose structures. The molecular basis of this enhancement has been investigated by determining crystal structures of DC-SIGN bound to a synthetic six-mannose fragment of a high mannose N-linked oligosaccharide, Manalpha1-2Manalpha1-3[Manalpha1-2Manalpha1-6]Manalpha1-6Man and to the disaccharide Manalpha1-2Man. The structures reveal mixtures of two binding modes in each case. Each mode features typical C-type lectin binding at the principal Ca2+-binding site by one mannose residue. In addition, other sugar residues form contacts unique to each binding mode. These results suggest that the affinity enhancement displayed toward oligosaccharides decorated with the Manalpha1-2Manalpha structure is due in part to multiple binding modes at the primary Ca2+ site, which provide both additional contacts and a statistical (entropic) enhancement of binding.

Selected figure(s)

Figure 1.
FIGURE 1. N-Linked high mannose structures. The full 9-mannose structure (Man[9]) is shown in the green box. The outer trimannose moiety, marked with a black box, is present in both the Man[6a] (red box) and Man[6b] (blue box) fragments.

Figure 2.
FIGURE 2. Electron density maps for bound ligands. The indicated bound ligand orientation is shown superimposed on the F[o] - F[c] electron density map (green, 2 contour) calculated from a model from which the indicated orientation was omitted but which included the alternative orientation. A, Man[6b] major orientation. B, Man[6b] minor orientation. C, Man[2] major orientation. D, Man[2] minor orientation.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 4202-4209) copyright 2007.

Figures were selected by an automated process.