The Crystal Structure of the Extracellular Domain of the Inhibitor Receptor Expressed on Myeloid Cells IREM-1

doi:10.1016/j.jmb.2007.01.011

Journal of Molecular Biology

Volume 367, Issue 2, 23 March 2007, Pages 310-318

https://doi.org/10.1016/j.jmb.2007.01.011 Get rights and content

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 Å 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.

Section snippets

Methods

Cloning, protein expression, purification, crystallization and X-ray data collection is reported elsewhere.¹⁸ The structure was solved using the molecular replacement program Phaser,¹⁹ and the coordinates of the mouse CLM-1 receptor extracellular domain (PDB code: 1ZOX) as the starting model. IREM-1 and CLM-1 immunoglobulin-like extracellular domains share 58.3% sequence identity. The molecular replacement search was carried out using data from 8–3.5 Å, and using space group P3₁21. Rigid-body

Acknowledgements

We thank Professor Roy Mariuzza (Center for Advanced Research in Biotechnology, Rockville, Maryland, USA) for critical reading of the manuscript. This work was supported, in part, by the Fondazione Gerolamo Galini (Genova, Italy). We thank Alessandro Faravelli (Laboratorio di Medicina Molecolare, Istituto Giannina Gaslini, Genova, Italy) for help during protein expression. We thank the constant scientific support from Professor Lorenzo Moretta (Istituto Giannina Gaslini, Genova, Italy).

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Journal of Molecular Biology

CommunicationThe Crystal Structure of the Extracellular Domain of the Inhibitor Receptor Expressed on Myeloid Cells IREM-1

Abstract

Section snippets

Methods

Acknowledgements

Trends Immunol.

Microbes Infect.

J. Mol. Biol.

J. Mol. Biol.

J. Biol. Chem.

Structure

Structure

Curr. Opin. Struct. Biol.

J. Struct. Biol.

J. Mol. Biol.

Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination

Annu. Rev. Immunol.

Immune inhibitory receptors

Science

Role of ITAM-containing adapter proteins and their receptors in the immune system and bone

Immunol. Rev.

Immunobiology of Toll-like receptors: emerging trends

Immunol. Cell Biol.

A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells

J. Expt. Med.

A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion

Mol. Cell Biol.

CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation

J. Immunol.

The CMRF-35H gene structure predicts for an independently expressed member of an ITIM/ITAM pair of molecules localized to human chromosome 17

Tissue Antigens

The CMRF-35 mAb recognizes a second leukocyte membrane molecule with a domain similar to the poly Ig receptor

Int. Immunol.

Molecular and functional characterization of IRp60, a member of the immunoglobulin superfamily that functions as an inhibitory receptor in human NK cells

Eur. J. Immunol.

Communication
The Crystal Structure of the Extracellular Domain of the Inhibitor Receptor Expressed on Myeloid Cells IREM-1