HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 20, 17140-17148, May 18, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/20/17140    most recent M009663200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cutrone, E. C. Articles by Langer, J. A. Search for Related Content PubMed PubMed Citation Articles by Cutrone, E. C. Articles by Langer, J. A. Social Bookmarking                      What's this?

Identification of Critical Residues in Bovine IFNAR-1 Responsible for Interferon Binding^*

Elizabeth Cali Cutrone and Jerome A. Langer^§

From the Department of Molecular Genetics & Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Interferons have antiviral, antigrowth and immunomodulatory effects. The human type I interferons, IFN-, IFN-, and IFN-, induce somewhat different cellular effects but act through a common receptor complex, IFNAR, composed of subunits IFNAR-1 and IFNAR-2. Human IFNAR-2 binds all type I IFNs but with lower affinity and different specificity than the IFNAR complex. Human IFNAR-1 has low intrinsic binding of human IFNs but strongly affects the affinity and differential ligand specificity of the IFNAR complex. Understanding IFNAR-1 interactions with the interferons is critical to elucidating the differential ligand specificity and activation by type I IFNs. However, studies of ligand interactions with human IFNAR-1 are compromised by its low affinity. The homologous bovine IFNAR-1 serendipitously binds human IFN-s with nanomolar affinity. Exploiting its strong binding of human IFN-2, we have identified residues important for ligand binding. Mutagenesis of any of five aromatic residues of bovine IFNAR-1 caused strong decreases in ligand binding, whereas mutagenesis of proximal neutral or charged residues had smaller effects. These residues were mapped onto a homology model of IFNAR-1 to identify the ligand-binding face of IFNAR-1, which is consistent with previous structure/function studies of human IFNAR-1. The topology of IFNAR-1/IFN interactions appears novel when compared with previously studied cytokine receptors.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. Kumaran, L. Wei, L. P. Kotra, and E. N. Fish A structural basis for interferon-{alpha}-receptor interactions FASEB J, October 1, 2007; 21(12): 3288 - 3296. [Abstract] [Full Text] [PDF]

				C. S. Rosenfeld, C.-S. Han, A. P. Alexenko, T. E. Spencer, and R. M. Roberts Expression of Interferon Receptor Subunits, IFNAR1 and IFNAR2, in the Ovine Uterus Biol Reprod, September 1, 2002; 67(3): 847 - 853. [Abstract] [Full Text] [PDF]