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PDBsum entry 2nms
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Immune system
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PDB id
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2nms
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References listed in PDB file
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Key reference
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Title
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The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells irem-1.
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Authors
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J.A.Márquez,
E.Galfré,
F.Dupeux,
D.Flot,
O.Moran,
N.Dimasi.
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Ref.
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J Mol Biol, 2007,
367,
310-318.
[DOI no: ]
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PubMed id
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Abstract
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The immune receptors expressed on myeloid cells (IREM) are type I transmembrane
proteins encoded on human chromosome 17 (17q25.1), whose function is believed to
be important in controlling inflammation. To date, three IREM receptors have
been identified. IREM-1 functions as an inhibitory receptor, whereas IREM-2 and
IREM-3 serve an activating function. Here, we report the crystal structure of
IREM-1 extracellular domain at 2.6 A resolution. The overall fold of IREM-1
resembles that of a V-type immunoglobulin domain, and reveals overall close
homology with immunoglobulin domains from other immunoreceptors such as CLM-1,
TREM-1, TLT-1 and NKp44. Comparing the surface electrostatic potential and
hydrophobicity of IREM-1 with its murine homologous CLM-1, we observed unique
structural properties for the complementary determining region of IREM-1, which
suggests that they may be involved in recognition of the IREM-1 ligand.
Particularly interesting is the structural conformation and physical properties
of the antibody's equivalent CDR3 loop, which we show to be a structurally
variable region of the molecule and therefore could be the main structural
determinant for ligand discrimination and binding. In addition, the analysis of
the IREM-1 structure revealed the presence of four structurally different
cavities. Three of these cavities form a continuous hydrophobic groove on the
IREM-1 surface, which point to a region of the molecule capable of accommodating
potential ligands.
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Figure 1.
Overall structure of IREM-1, features of the extended protrusion and
comparison with CLM-1. (a) A ribbon representation of the IREM-1
structure. IREM-1 has the expected V-set Ig domain fold present in the
immunoglobulins. The secondary structure elements (β-strands and
the 310 α-helix) were defined using the program
DSSP.41 The
antibody's equivalent CDR loops (CDReq) are shown in red and are
labelled. Disulphide bonds are shown and are labelled with their
respective cysteine residues. In this ribbon representation and in all
the subsequent diagrams, N and C denote the amino terminus and the
carboxy terminus of the protein chain. The location of the potential
N-glycosylation site, which involves asparagine 88, is shown with a
red diamond. (b) An important feature of the IREM-1 structure is the
formation of a prominent protrusion that extends from the main
immunoglobulin body. This protrusion is about 18 Å long,
15 Å wide and 11 Å deep. As seen in this Figure,
the top of this protrusion is blocked, in part, by the side-chains of
tryptophan 59, aspartate 116 and glutamate 111. The other amino acid
residues present at this protrusion are isoleucine 64, lysine 67,
tryptophan 52 and tryptophan 107. (c) Superimposition of IREM-1 with
its murine homologous CLM-1 gives an rmsd of 1.06 for all the
structurally equivalent Cα atoms forming the core of the
immunoglobulin-like domain (102 residues). The orientation of IREM-1
and CLM-1 here is equivalent to that in (a). In this superimposition
diagram, IREM-1 is in blue and CLM-1 is in red. The β-hairpin
formed by β-strands C-C′ is labelled. The location of the
CDReq loops is shown schematically. The circle highlights the
prominent structural difference of the CDReq3 between IREM-1 and
CLM-1.
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Figure 4.
Figure 4. Cavities on IREM-1. The cavities on IREM-1 are
shown as yellow dots and are labelled from 1 to 4. The locations
of the CDReq loops are shown schematically and are labelled only
in the ribbon diagram. In (b) and (d) the continuous groove
formed by cavities 1, 2 and 3 is highlighted. This groove, which
possesses a negative potential and is highly hydrophobic, may
accommodate potential ligands. The electrostatic potential
surfaces and hydrophobicity are coloured as in Figure 3. The
ribbon orientation is equivalent to that of Figure 1(a).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
367,
310-318)
copyright 2007.
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