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

J. Biol. Chem., Vol. 281, Issue 10, 6642-6647, March 10, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/10/6642    most recent M513118200v2 M513118200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lorenzen, I. Articles by Grötzinger, J. Search for Related Content PubMed PubMed Citation Articles by Lorenzen, I. Articles by Grötzinger, J. Social Bookmarking                      What's this?

The Structure of the Interleukin-15 Receptor and Its Implications for Ligand Binding^*

Inken Lorenzen, Andrew J. Dingley, Yannick Jacques^¶, and Joachim Grötzinger¹

From the Biochemisches Institut der Christian-Albrechts-Universität Kiel, Olshausenstrasse 40, 24118 Kiel, Germany, Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom, and ^¶INSERM, UMR 601, Groupe de Recherche Cytokines et Récepteurs, Institut de Biologie, Nantes F-44093, France

Interleukin (IL)-15 is a member of the small four -helix bundle family of cytokines. IL-15 was discovered by its ability to mimic IL-2-mediated T-cell proliferation. Both cytokines share the and receptor chains of the IL-2 receptor for signal transduction. However, in addition, they target specific chain receptors IL-15R and IL-2R, respectively. The exceptionally high affinity binding of IL-15 to IL-15R is mediated by its sushi domain. Here we present the solution structure of the IL-15R sushi domain solved by NMR spectroscopy and a model of its complex with IL-15. The model shows that, rather than the familiar hydrophobic forces dominating the interaction interface between cytokines and their cognate receptors, the interaction between the IL-15 and IL-15R complex involves a large network of ionic interactions. This type of interaction explains the exceptionally high affinity of the IL-15·IL-15R complex, which is essential for the biological effects of this important cytokine and which is not observed in other cytokine/cytokine receptor complexes.

Received for publication, December 8, 2005

The atomic coordinates and structure factors (code 2ERS) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by a grant of the Deutsche Forschungsgemeinschaft (SFB 415). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Biochemisches Institut, Christian-Albrechts-Universität Kiel, Olshausenstr. 40, D-24118 Kiel, Germany. Tel.: 49-431-8801686; Fax: 49-431-8805007; E-mail: jgroetzinger{at}biochem.uni-kiel.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. P. Carroll, V. Paunovic, and M. Gadina Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity Rheumatology, September 1, 2008; 47(9): 1269 - 1277. [Abstract] [Full Text] [PDF]

				E. H. Duitman, Z. Orinska, E. Bulanova, R. Paus, and S. Bulfone-Paus How a Cytokine Is Chaperoned through the Secretory Pathway by Complexing with Its Own Receptor: Lessons from Interleukin-15 (IL-15)/IL-15 Receptor {alpha} Mol. Cell. Biol., August 1, 2008; 28(15): 4851 - 4861. [Abstract] [Full Text] [PDF]

				S. K. Olsen, N. Ota, S. Kishishita, M. Kukimoto-Niino, K. Murayama, H. Uchiyama, M. Toyama, T. Terada, M. Shirouzu, O. Kanagawa, et al. Crystal Structure of the Interleukin-15{middle dot}Interleukin-15 Receptor {alpha} Complex: INSIGHTS INTO TRANS AND CIS PRESENTATION J. Biol. Chem., December 21, 2007; 282(51): 37191 - 37204. [Abstract] [Full Text] [PDF]

				M. Rafei, J. H. Wu, B. Annabi, L. Lejeune, M. Francois, and J. Galipeau A GMCSF and IL-15 fusokine leads to paradoxical immunosuppression in vivo via asymmetrical JAK/STAT signaling through the IL-15 receptor complex Blood, March 1, 2007; 109(5): 2234 - 2242. [Abstract] [Full Text] [PDF]

				M. P. Rubinstein, M. Kovar, J. F. Purton, J.-H. Cho, O. Boyman, C. D. Surh, and J. Sprent Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha} PNAS, June 13, 2006; 103(24): 9166 - 9171. [Abstract] [Full Text] [PDF]