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PDBsum entry 1sl6
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Sugar binding protein
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PDB id
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1sl6
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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 distinct ligand-Binding and targeting properties of the receptors dc-Sign and dc-Signr.
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Authors
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Y.Guo,
H.Feinberg,
E.Conroy,
D.A.Mitchell,
R.Alvarez,
O.Blixt,
M.E.Taylor,
W.I.Weis,
K.Drickamer.
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Ref.
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Nat Struct Mol Biol, 2004,
11,
591-598.
[DOI no: ]
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PubMed id
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Abstract
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Both the dendritic cell receptor DC-SIGN and the closely related endothelial
cell receptor DC-SIGNR bind human immunodeficiency virus and enhance infection.
However, biochemical and structural comparison of these receptors now reveals
that they have very different physiological functions. By screening an extensive
glycan array, we demonstrated that DC-SIGN and DC-SIGNR have distinct
ligand-binding properties. Our structural and mutagenesis data explain how both
receptors bind high-mannose oligosaccharides on enveloped viruses and why only
DC-SIGN binds blood group antigens, including those present on microorganisms.
DC-SIGN mediates endocytosis, trafficking as a recycling receptor and releasing
ligand at endosomal pH, whereas DC-SIGNR does not release ligand at low pH or
mediate endocytosis. Thus, whereas DC-SIGN has dual ligand-binding properties
and functions both in adhesion and in endocytosis of pathogens, DC-SIGNR binds a
restricted set of ligands and has only the properties of an adhesion receptor.
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Figure 2.
Figure 2. Oligosaccharides used in structural studies of DC-SIGN
and DC-SIGNR. Symbols are as defined in Figure 1. Structures
of the complexes of both proteins with the GlcNAc[2]Man[3]
oligosaccharide are as described^14. This oligosaccharide
contains a branch mannose that is not linked to other sugars.
The branch mannose residues in the high-mannose oligosaccharide
are linked in either  (outer
branch) or  (core
branch) configuration. The Man[4] oligosaccharide is an analog
of the outer branch structure.
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Figure 4.
Figure 4. DC-SIGN and DC-SIGNR interactions with Lewisx and
oligomannosides. (a) DC-SIGNR bound to Lewisx trisaccharide.
(b) DC-SIGN bound to LNFP III. In a and b, key residues that
differ between DC-SIGN and DC-SIGNR are shown. (c) Comparison of
Man[4] (yellow bonds) binding with GlcNAc[2]Man[3] (red
bonds)14. Phe313 interacts with the Man 1-6Man
moiety of the trimannose structure. (d) Comparison of Man[4]
(yellow bonds) and LNFP III (black bonds) bound to DC-SIGN. The
color scheme is the same as in Figure 3.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2004,
11,
591-598)
copyright 2004.
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