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PDBsum entry 2zg3
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Immune system/carbohydrate binding prote
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PDB id
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2zg3
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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 implications of siglec-5-Mediated sialoglycan recognition.
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Authors
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M.A.Zhuravleva,
K.Trandem,
P.D.Sun.
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Ref.
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J Mol Biol, 2008,
375,
437-447.
[DOI no: ]
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PubMed id
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Abstract
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Sialic acid (Sia) Ig-like binding lectins are important mediators of recognition
and signaling events among myeloid cells. To investigate the molecular mechanism
underlying sialic acid Ig-like lectin (Siglec) functions, we determined the
crystal structure of the two N-terminal extracellular domains of human myeloid
cell inhibitory receptor Siglec-5 (CD170) and its complexes with two sialylated
carbohydrates. The native structure revealed an unusual conformation of the CC'
ligand specificity loop and a unique interdomain disulfide bond. The alpha(2,3)-
and alpha(2,6)-sialyllactose complexed structures showed a conserved Sia
recognition motif that involves both Arg124 and a portion of the G-strand in the
V-set domain forming beta-sheet-like hydrogen bonds with the glycerol side chain
of the Sia. Only few protein contacts to the subterminal sugars are observed and
mediated by the highly variable GG' linker and CC' loop. These structural
observations, in conjunction with surface plasmon resonance binding assays,
provide mechanistic insights into linkage-dependent Siglec carbohydrate
recognition and suggest that Siglec-5 and other CD33-related Siglec receptors
are more promiscuous in sialoglycan recognition than previously understood.
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Figure 4.
Fig. 4. Siglec-5 in complex with (a) α(2,3)-sialyllactose
and (b) α(2,6)-sialyllactose. Sections of the unbiased (before
the inclusion of the ligand) |F[o]| − |F[c]| electron density
maps contoured at 2 σ are shown in the left panels. Siglec-5 is
shown in a ribbon diagram (green), with the Arg124 depicted in
the balls and sticks. The carbohydrate moieties are in yellow.
Interactions between the respective receptor and carbohydrate at
the binding site are shown in the right panels. Direct
protein–ligand interactions with the Sia and the galactose are
shown in red and blue, respectively. Water-mediated interactions
are in green. (c) Superposition of the ligand binding sites of
the sialoadhesin (gray) and Siglec-5 (green) in their complex
structures with α(2,3)-sialyllactose. Residues corresponding to
sialoadhesin are given in parentheses.
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Figure 5.
Fig. 5. (a) A schematic diagram featuring differences in the
G-strand (red) between classic V-set Ig fold (left panel) and
Siglec-specific Ig fold (right panel). Sia is shown as a
β-strand (green). (b) Schematic representation of conserved
main chain interactions between Siglec CFG β-sheet and Sia
(green). The mode in which Sia interacts with main chain atoms
on the G-strand mimics hydrogen bond interactions (dashed lines)
in classic antiparallel pleated β-sheet.
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The above figures are
reprinted
from an Open Access publication published by Elsevier:
J Mol Biol
(2008,
375,
437-447)
copyright 2008.
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