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

J. Biol. Chem., Vol. 283, Issue 46, 32143-32151, November 14, 2008

This Article Free via Author's Choice: AC AC Full Text Full Text (PDF) Supplemental Data AC All Versions of this Article: 283/46/32143    most recent M804846200v1 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 Papic, N. Articles by Howard, J. C. Search for Related Content PubMed PubMed Citation Articles by Papic, N. Articles by Howard, J. C. Social Bookmarking                      What's this?

Inactive and Active States of the Interferon-inducible Resistance GTPase, Irga6, in Vivo^*

Natasa Papic, Julia P. Hunn, Nikolaus Pawlowski, Jens Zerrahn¹, and Jonathan C. Howard²

From the Department of Cell Genetics, Institute for Genetics, University of Cologne, 50674 Cologne, Germany and the Department of Immunology, Max-Planck-Institute for Infection Biology, Schumannstrasse 21-22, 10117 Berlin, Germany

Irga6, a myristoylated, interferon-inducible member of the immunity-related GTPase family, contributes to disease resistance against Toxoplasma gondii in mice. Accumulation of Irga6 on the T. gondii parasitophorous vacuole membrane is associated with vesiculation and ultimately disruption of the vacuolar membrane in a process that requires an intact GTP-binding domain. The role of the GTP-binding domain of Irga6 in pathogen resistance is, however, unclear. We provide evidence that Irga6 in interferon-induced, uninfected cells is predominantly in a GDP-bound state that is maintained by other interferon-induced proteins. However, Irga6 that accumulates on the parasitophorous vacuole membrane after Toxoplasma infection is in the GTP-bound form. We demonstrate that a monoclonal antibody, 10D7, specifically detects GTP-bound Irga6, and we show that the formation of the 10D7 epitope follows from a GTP-dependent conformational transition of the N terminus of Irga6, anticipating an important role of the myristoyl group on Irga6 function in vivo.

Received for publication, June 25, 2008 , and in revised form, September 10, 2008.

^* This study was supported by Deutsche Forschungsgemeinschaft Grants SPP1110, SFB635, and SFB670 and by the University of Cologne. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

¹ Present address: Institute of Clinical Pharmacology PAREXEL International GmbH, 14050 Berlin, Germany.

Author's Choice—Final version full access.

Author's Choice

Creative Commons Attribution Non-Commercial License applies to Author Choice Articles

² To whom correspondence should be addressed: Institute for Genetics, University of Cologne, Zülpicher Str. 47, 50674 Cologne, Germany. Tel.: 49-2214704864; Fax: 49-2214706749; E-mail: j.howard{at}uni-koeln.de.

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

This article has been cited by other articles:

				Y. Zhao, D. J. P. Ferguson, D. C. Wilson, J. C. Howard, L. D. Sibley, and G. S. Yap Virulent Toxoplasma gondii Evade Immunity-Related GTPase-Mediated Parasite Vacuole Disruption within Primed Macrophages J. Immunol., March 15, 2009; 182(6): 3775 - 3781. [Abstract] [Full Text] [PDF]