Radiation inactivation of human γ-interferon: Cellular activation requires two dimers

Jerome A. Langer, Abbas Rashidbaigi, Gianni Garotta, Ellis Kempner

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

γ-Interferon (IFN-γ) is a 17-kDa broad-spectrum cytokine which exerts its effects on a variety of target cells through its interaction with the IFN-γ receptor. Although physicochemical studies of Escherichia coli- derived IFN-γ, as well as its crystal structure, demonstrate that it is a homodimer in solution (M(r) 34,000), previous radiation inactivation studies yielded a functional size for IFN-γ of 63-73 kDa in an antiviral assay. To understand the relationship between the solution form of IFN-γ and the moiety that actually binds to the cellular receptor and activates cells, we examined irradiated nonradioactive and 32P-labeled IFN-γ for its migration in SDS/polyacrylamide gels (to determine its physical integrity), its binding to cells, its reactivity in an ELISA, and its antiviral activity. The functional size of IFN-γ differed in the assays, being 22 ± 2 kDa for the physical destruction of IFN-γ, 56 ± 2 kDa for the cellular binding assay, 45-50 kDa for reactivity in the ELISA, and 72 ± 6 kDa for antiviral activity. The results from the binding assays constitute direct evidence that IFN-γ binds to its cellular receptor as a dimer. However, for antiviral activity, the functional mass is equivalent to a tetramer. This is consistent with models involving ligand-induced receptor dimerization, whereby two dimers acting in concert (equivalent to the target size of a tetramer) are required to activate cells in the antiviral assay.

Original languageEnglish (US)
Pages (from-to)5818-5822
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number13
DOIs
StatePublished - Jun 21 1994

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • receptor
  • target size

Fingerprint Dive into the research topics of 'Radiation inactivation of human γ-interferon: Cellular activation requires two dimers'. Together they form a unique fingerprint.

  • Cite this