Crystal structure of human interferon‐γ receptor 2 reveals the structural basis for receptor specificity. Issue 9 (1st September 2016)

• Record Type: Journal Article
• Authors: Mikulecký, Pavel; Zahradník, Jirí; Kolenko, Petr; Černý, Jiří; Charnavets, Tatsiana; Kolářová, Lucie; Nečasová, Iva; Pham, Phuong Ngoc; Schneider, Bohdan
• Is Part Of: Acta crystallographica. Volume 72:Issue 9(2016)
• Page Start: 1017
• Page End: 1025
• Publication Date: 2016-09-01
• Subjects: interferon‐γ receptor 2 -- fibronectin type III domain -- class 2 cytokine receptors; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798316012237
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : 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. Abstract : Interferon‐γ receptor 2 is a cell‐surface receptor that is required for interferon‐γ signalling and therefore plays a critical immunoregulatory role in innate and adaptive immunity against viral and also bacterial and protozoal infections. A crystal structure of the extracellular part of human interferon‐γ receptor 2 (IFNγR2) was solved by molecular replacement at 1.8 Å resolution. Similar to other class 2 receptors, IFNγR2 has two fibronectin type III domains. The characteristic structural features of IFNγR2 are concentrated in its N‐terminal domain: an extensive π–cation motif of stacked residues KWRWRH, a NAG–W–NAG sandwich (where NAG stands for N ‐acetyl‐d ‐glucosamine) and finally a helix formed by residues 78–85, which is unique among class 2 receptors. Mass spectrometry and mutational analyses showed the importance of N‐linked glycosylation to the stability of the protein and confirmed the presence of two disulfide bonds. Structure‐based bioinformatic analysis revealed independent evolutionary behaviour of both receptor domains and, together with multiple sequence alignment, identified putative binding sites for interferon‐γ and receptor 1, the ligands of IFNγR2.