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Crystal structure of human interferon‐γ receptor 2 reveals the structural basis for receptor specificity
Author(s) -
Mikulecký Pavel,
Zahradník Jirí,
Kolenko Petr,
Černý Jiří,
Charnavets Tatsiana,
Kolářová Lucie,
Nečasová Iva,
Pham Phuong Ngoc,
Schneider Bohdan
Publication year - 2016
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798316012237
Subject(s) - receptor , interferon , biology , interleukin 13 receptor , glycosylation , interleukin 21 receptor , innate immune system , protease activated receptor 2 , protein structure , microbiology and biotechnology , 5 ht5a receptor , biochemistry , genetics , insulin like growth factor 1 receptor , growth factor
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.