Crystal structure of human interferon-? receptor 2 reveals the structural basis for receptor specificity.

ABSTRACT: Interferon-? receptor 2 is a cell-surface receptor that is required for interferon-? 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-? receptor 2 (IFN?R2) was solved by molecular replacement at 1.8?Å resolution. Similar to other class 2 receptors, IFN?R2 has two fibronectin type III domains. The characteristic structural features of IFN?R2 are concentrated in its N-terminal domain: an extensive ?-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-? and receptor 1, the ligands of IFN?R2.

SUBMITTER: Mikulecky P 

PROVIDER: S-EPMC5013595 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature