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PDBsum entry 2d3v
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Immune system
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PDB id
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2d3v
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the human monocyte-Activating receptor, &Quot;group 2" leukocyte ig-Like receptor a5 (lilra5/lir9/ilt11).
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Authors
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M.Shiroishi,
M.Kajikawa,
K.Kuroki,
T.Ose,
D.Kohda,
K.Maenaka.
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Ref.
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J Biol Chem, 2006,
281,
19536-19544.
[DOI no: ]
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PubMed id
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Abstract
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Human leukocyte Ig-like receptor B1 (LILRB1) and B2 (LILRB2) belong to
"Group 1" receptors and recognize a broad range of major
histocompatibility complex class I molecules (MHCIs). In contrast, "Group
2" receptors show low similarity with LILRB1/B2, and their ligands remain
to be identified. To date, the structural and functional characteristics of
Group 2 LILRs are poorly understood. Here we report the crystal structure of the
extracellular domain of LILRA5, which is an activating Group 2 LILR expressed on
monocytes and neutrophils. Unexpectedly, the structure showed large changes in
structural conformation and charge distribution in the region corresponding to
the MHCI binding site of LILRB1/B2, which are also distinct from killer cell
Ig-like receptors and Fc alpha receptors. These changes probably confer the
structural hindrance for the MHCI binding, and their key amino acid
substitutions are well conserved in Group 2 LILRs. Consistently, the surface
plasmon resonance and flow cytometric analyses demonstrated that LILRA5
exhibited no affinities to all tested MHCIs. These results raised the
possibility that LILRA5 as well as Group 2 LILRs do not play a role in any MHCI
recognition but could possibly bind to non-MHCI ligand(s) on the target cells to
provide a novel immune regulation mechanism.
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Figure 1.
FIGURE 1. Crystal structure of the LILRA5 extracellular
domain. A, ribbon drawing of the structure of LILRA5 in a
rainbow color scheme from blue (N-terminal) to red (C-terminal).
The dotted lines represent the disordered residues of loop
regions (residues 106-116 and 136-138). The star indicates the
predicted N-linked glycosylation site. B, topological diagram of
LILRA5 structure. The arrows show the direction of the  -strands.
Cylinders labeled PP show polyproline II-type helices. C, left,
overall view of domain 2 of LILRA5 (magenta) superimposed on
LILRB1 (yellow). The region between 106 and 116 is disordered.
Right, close-up view of the box in the left panel. LILRA5 and
LILRB1 are shown in magenta and yellow stick models,
respectively. Hydrogen bonds made between A' and G strands are
shown in green dashed lines. The green dotted circle indicates
the residue 105 following the disordered loop of LILRA5. The
black dotted circle indicates the C-terminal residue of LILRA5
unable to form the A'GFCC' -sheet due to the
distortion caused by Pro^194 (see text).
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Figure 3.
FIGURE 3. Structural comparison of MHCI binding sites
between LILRBs and LILRA5. A, center, the LILRB1 (light pink) of
the HLA-A2 complex model (4) (heavy chain; blue, 2-microglobulin; cyan)
is superimposed onto LILRA5 (red). Left and right, large
structural difference observed in D1 (right, orange dotted
circle around the C' strand) and D2 (right, blue dotted circle
around the DE loop). LILRB1 (light pink) and LILRB2 (light
green) are superimposed onto LILRA5 (red). B, the ribbon model
of CC' sheet of LILRA5 (red) is superimposed onto those (C
strand and 3[10] helices) of LILRB1 (light pink). Conserved
amino acids are shown in a ball model (left), and their colors
are the same as those in amino acid comparison among LILR
members (right). Key amino acids for structural changes are
colored, and this coloring is also applied in the labels in C.
The characters, h and s, on the sequence alignment indicate
helix and sheet structures, respectively. C, details of local
structures around the 3[10] helix of LILRB1 (left) and C' sheet
of LILRA5 (right), highlighted by the orange dotted circle in A.
The black dotted lines are shown in order for the main-chain
structures to be easily recognized. The hydrophobic core of
LILRB1 (left) and hydrophobic pocket of LILRA5 (right) are
indicated by the red dotted circles.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
19536-19544)
copyright 2006.
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