PDBsum entry 2nms

Immune system

PDB id: 2nms

Contents

Protein chain

112 a.a. *

Waters ×50

* Residue conservation analysis

PDB id:

2nms

Name:

Immune system

Title:

The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells irem-1

Structure:

Cmrf35-like-molecule 1. Chain: a. Fragment: ectodomain, residues 21-140. Synonym: clm-1, immune receptor expressed on myeloid cells protein 1, irem-1, immunoglobulin superfamily member 13, nk inhibitory receptor, cd300 antigen like family member f, igsf13, irem-1 myeloid receptor extracellular domain 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: myeloid cells. Gene: cd300lf, clm1, igsf13, irem1, nkir. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.218 R-free: 0.255

Authors:

N.Dimasi,J.A.Marquez

Key ref:

J.A.Márquez et al. (2007). The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells IREM-1. J Mol Biol, 367, 310-318. PubMed id: 17275839 DOI: 10.1016/j.jmb.2007.01.011

Date:

23-Oct-06 Release date: 07-Nov-06

Protein chain

Q8TDQ1  (CLM1_HUMAN) -  CMRF35-like molecule 1 from Homo sapiens

Seq: 290 a.a.

Struc: 112 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2007.01.011

J Mol Biol 367:310-318 (2007)

PubMed id: 17275839

The crystal structure of the extracellular domain of the inhibitor receptor expressed on myeloid cells IREM-1.

J.A.Márquez, E.Galfré, F.Dupeux, D.Flot, O.Moran, N.Dimasi.

ABSTRACT

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.

Selected figure(s)

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.

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).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 367, 310-318) copyright 2007.

Figures were selected by the author.