Crystal structure of human interferon-γ receptor 2 reveals the structural basis for receptor specificity.
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.
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Pavel
P
Mikulecký
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Jirí
J
Zahradník
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Petr
P
Kolenko
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Jiří
J
Černý
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Tatsiana
T
Charnavets
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Lucie
L
Kolářová
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Iva
I
Nečasová
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Phuong Ngoc
PN
Pham
Institute of Biotechnology CAS, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
Bohdan
B
Schneider
D020816:Amino Acid Motifs; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D000072417:Protein Domains; D017510:Protein Folding; D055550:Protein Stability; D017471:Receptors, Interferon / Q000737:chemistry*
D004220:Disulfides; C086185:IFNGR2 protein, human; D017471:Receptors, Interferon
class 2 cytokine receptors; fibronectin type III domain; interferon-γ receptor 2