Crystal Structure of Human Interferon-γ1 in Complex with Its High-Affinity Receptor Interferon-γR1

Zachary J. Miknis, Eugenia Magracheva, Wei Li, Alexander Zdanov, Sergei V. Kotenko, Alexander Wlodawer

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Interferon (IFN)-γ1 [also known as interleukin (IL)-29] belongs to the recently discovered group of type III IFNs. All type III IFNs initiate signaling processes through formation of specific heterodimeric receptor complexes consisting of IFN-γR1 and IL-10R2. We have determined the structure of human IFN-γ1 complexed with human IFN-γR1, a receptor unique to type III IFNs. The overall structure of IFN-γ1 is topologically similar to the structure of IL-10 and other members of the IL-10 family of cytokines. IFN-γR1 consists of two distinct domains having fibronectin type III topology. The ligand-receptor interface includes helix A, loop AB, and helix F on the IFN site, as well as loops primarily from the N-terminal domain and inter-domain hinge region of IFN-γR1. Composition and architecture of the interface that includes only a few direct hydrogen bonds support an idea that long-range ionic interactions between ligand and receptor govern the process of initial recognition of the molecules while hydrophobic interactions finalize it.

Original languageEnglish (US)
Pages (from-to)650-664
Number of pages15
JournalJournal of molecular biology
Volume404
Issue number4
DOIs
StatePublished - Dec 10 2010

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • Antiviral
  • Crystallography
  • Cytokine
  • Immunity
  • Signaling

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