NDLI: Differences in Activity between α and β Type I Interferons Explored by Mutational Analysis

Content Provider	Journal of Biological Chemistry (JBC)
Author	Runkel, Laura Pfeffer, Lawrence Lewerenz, Malte Monneron, Danielle Yang, Chuan He Murti, Aruna Pellegrini, Sandra Goelz, Susan Uzé, Gilles Mogensen, Knud
Abstract	Type I interferon (IFN) subtypes α and β share a common multicomponent, cell surface receptor and elicit a similar range of biological responses, including antiviral, antiproliferative, and immunomodulatory activities. However, α and β IFNs exhibit key differences in several biological properties. For example, IFN-β, but not IFN-α, induces the association of tyrosine-phosphorylated receptor components ifnar1 and ifnar2, and has activity in cells lacking the IFN receptor-associated, Janus kinase tyk2. To define the structural basis for these functional differences we produced human IFN-β with point mutations and compared them to wild-type IFN-β in assays that distinguish α and β IFN subtypes. IFN-β mutants with charged residues (N86K, N86E, or Y92D) introduced at two positions in the C helix lost the ability to induce the association of tyrosine-phosphorylated receptor chains and had reduced activity on tyk2-deficient cells. The combination of negatively charged residues N86E and Y92D (homologous with IFN-α8) increased the cross-species activity of the mutant IFN-βs on bovine cells to a level comparable to that of human IFN-αs. In contrast, point mutations in the AB loop and D helix had no significant effect on these subtype-specific activities. A subset of these latter mutations did, however, reduce activity in a manner analogous to IFN-α mutations. The effects of these mutations on IFN-β activity are discussed in the context of a family of related ligands acting through a common receptor and signaling pathway.
Related Links	http://www.jbc.org/content/273/14/8003.abstract
Ending Page	8008
Starting Page	8003
Page Count	6
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	14
Volume Number	273
DOI	10.1074/jbc.273.14.8003
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	1998-04-03
Access Restriction	Open
Subject Keyword	PROTEIN CHEMISTRY AND STRUCTURE
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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