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PDBsum entry 1k9i
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Sugar binding protein
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PDB id
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1k9i
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis for selective recognition of oligosaccharides by dc-Sign and dc-Signr.
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Authors
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H.Feinberg,
D.A.Mitchell,
K.Drickamer,
W.I.Weis.
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Ref.
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Science, 2001,
294,
2163-2166.
[DOI no: ]
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PubMed id
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Abstract
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Dendritic cell specific intracellular adhesion molecule-3 (ICAM-3) grabbing
nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic
cells, mediates the initial interaction of dendritic cells with T cells by
binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the
endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to
oligosaccharides that are present on the envelope of human immunodeficiency
virus (HIV), an interaction that strongly promotes viral infection of T cells.
Crystal structures of carbohydrate-recognition domains of DC-SIGN and of
DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal
that these receptors selectively recognize endogenous high-mannose
oligosaccharides and may represent a new avenue for developing HIV prophylactics.
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Figure 1.
Fig. 1. Oligosaccharide structures. (A) The pentasaccharide
co-crystallized with both DC-SIGN and DC-SIGNR. Residue numbers
used in the text are shown in parentheses. (B) N-linked
high-mannose structure. The full nine-mannose structure (Man[9])
is shown, but the presence of  1-2 linked
mannose at the branch termini is variable. The inner branched
trimannose structure Man 1-3 [Man
1-6]Man is
shown in the red box, and the outer trimannose structure is
shown in the yellow box. (C) Typical N-linked complex
carbohydrate. The portion equivalent to the pentasaccharide used
in this study is boxed in red. The inner trimannose structure is
common to both complex and high-mannose N-linked
oligosaccharides. Gal, galactose; GlcNAc, N-acetylglucosamine;
Man, mannose; Sia, sialic acid.
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Figure 4.
Fig. 4. A phenylalanine prevents binding of the inner
trimannosyl core of N-linked oligosaccharides. The DC-SIGNR CRD
is shown in cyan, with the Phe^325 side chain in a
ball-and-stick representation. In yellow-green, the outer
branched trimannose structure of Man[9] was superimposed on the
trimannose structure seen in the DC-SIGNR crystals. For clarity,
only the 1-6 branch
is shown. In magenta, the mannose residue of a model of the
internal Man  1-4GlcNAc
1-4GlcNAc
moiety of N-linked oligosaccharides was superimposed on the
central (reducing) mannose of the trimannose structure. The
model was made by setting the torsion angles of the glycosidic
linkages to their average values found in an oligosaccharide
structure database (13), with adjustments in the torsion angles
to overlay the branched trimannose structure precisely. The
clash of the first GlcNAc with Phe^325 is evident. In both the
positions of the 1-3 and
1-6 linked
mannose residues linked to the central mannose of the trimannose
structure are indicated in the black text.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2001,
294,
2163-2166)
copyright 2001.
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