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PDBsum entry 2it5
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Immune system
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PDB id
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2it5
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References listed in PDB file
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Key reference
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Title
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Multiple modes of binding enhance the affinity of dc-Sign for high mannose n-Linked glycans found on viral glycoproteins.
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Authors
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H.Feinberg,
R.Castelli,
K.Drickamer,
P.H.Seeberger,
W.I.Weis.
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Ref.
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J Biol Chem, 2007,
282,
4202-4209.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
4202-4209)
copyright 2007.
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