Research Article: Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity

Date Published: September 01, 2016

Publisher: International Union of Crystallography

Author(s): Pavel Mikulecký, Jirí Zahradník, Petr Kolenko, Jiří Černý, Tatsiana Charnavets, Lucie Kolářová, Iva Nečasová, Phuong Ngoc Pham, Bohdan Schneider.


The structure of the extracellular portion of interferon-γ receptor 2, a member of the class II cytokine receptors, has been solved. Bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and identified a putative binding site for interferon-γ.

Partial Text

Interferon-γ receptor 2 is a cell-surface receptor that represents a crucial molecule in the interferon-γ (IFNγ) signalization pathway, influencing innate and adaptive immunity against pathogens and tumours (Schoenborn & Wilson, 2007 ▸; Lin & Young, 2013 ▸). The signalling cascade is initiated by the binding of IFNγ to its high-affinity cell surface receptor 1, forming a binary complex with a structure that has already been determined [PDB entries 1fg9 (Thiel et al., 2000 ▸) and 1fyh (Landar et al., 2000 ▸)]. However, to activate this binary complex and activate the JAK/STAT signalization pathway (Jung et al., 1987 ▸; Cook et al., 1994 ▸; Hemmi et al., 1994 ▸), IFNγ receptor 2 must participate in a ternary complex created by a homodimer of IFNγ, two molecules of receptor 1 and molecule(s) of receptor 2. To date, detailed structural and biophysical characterization of IFNγ receptor 2, the key molecule for proper IFNγ signalization, is lacking.

A partially deglycosylated extracellular part of the interferon-γ receptor 2, IFNγR2, was crystallized and its structure was determined at 1.8 Å resolution and deposited in the PDB with accession code 5eh1. The electron-density map was interpreted for amino-acid residues 28–240, apart from two short loops. The IFNγR2 structure revealed the fold common to other cytokine receptors: two fibronectin type III domains connected by a short linker. IFNγR2 is a glycoprotein with five of the six potential N-linked glycosylation sites glycosyl­ated, as confirmed by mass spectrometry and the crystal structure. Our analysis of glycosylation also uncovers the role of the oligosaccharide moieties at Asn110 and Asn137, which sandwich Trp131 and shield its hydrophobic aromatic ring from the solvent. Both potential disulfide bonds form but are not critical for the stability of IFNγR2, as it is also stable in a reducing environment. The fifth cysteine Cys174 is bound to the monomeric cysteine.

The following references are cited in the Supporting Information for this article: Cancino-Díaz et al. (2002 ▸), Černý et al. (2007 ▸), Furche et al. (2014 ▸), O’Boyle et al. (2011 ▸) and Rüger et al. (2015 ▸).