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

J. Biol. Chem., Vol. 283, Issue 26, 17827-17837, June 27, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/26/17827    most recent M800866200v1 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 Google Scholar Google Scholar Articles by Siroy, A. Articles by Niederweis, M. Search for Related Content PubMed PubMed Citation Articles by Siroy, A. Articles by Niederweis, M. Social Bookmarking                      What's this?

Rv1698 of Mycobacterium tuberculosis Represents a New Class of Channel-forming Outer Membrane Proteins^*

Axel Siroy¹, Claudia Mailaender¹, Daniel Harder^¶, Stephanie Koerber^||, Frank Wolschendorf, Olga Danilchanka, Ying Wang, Christian Heinz, and Michael Niederweis²

From the Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, the Lehrstuhl für Mikrobiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstrasse 5, D-91058 Erlangen, Germany, the ^||Institut für Biophysikalische Chemie, Johann-Wolfgang-Goethe-Universität, Max-von-Laue Strasse 9, 60438 Frankfurt am Main, Germany, and the ^¶Lehrstuhl für Ernährungsphysiologie, Wissenschaftszentrum Weihenstephan, Technische Universität München, Am Forum 5, 85350 Freising, Germany

Mycobacteria contain an outer membrane composed of mycolic acids and a large variety of other lipids. Its protective function is an essential virulence factor of Mycobacterium tuberculosis. Only OmpA, which has numerous homologs in Gram-negative bacteria, is known to form channels in the outer membrane of M. tuberculosis so far. Rv1698 was predicted to be an outer membrane protein of unknown function. Expression of rv1698 restored the sensitivity to ampicillin and chloramphenicol of a Mycobacterium smegmatis mutant lacking the main porin MspA. Uptake experiments showed that Rv1698 partially complemented the permeability defect of the M. smegmatis porin mutant for glucose. These results indicated that Rv1698 provides an unspecific pore that can partially substitute for MspA. Lipid bilayer experiments demonstrated that purified Rv1698 is an integral membrane protein that indeed produces channels. The main single channel conductance is 4.5 ± 0.3 nanosiemens in 1 M KCl. Zero current potential measurements revealed a weak preference for cations. Whole cell digestion of recombinant M. smegmatis with proteinase K showed that Rv1698 is surface-accessible. Taken together, these experiments demonstrated that Rv1698 is a channel protein that is likely involved in transport processes across the outer membrane of M. tuberculosis. Rv1698 has single homologs of unknown functions in Corynebacterineae and thus represents the first member of a new class of channel proteins specific for mycolic acid-containing outer membranes.

Received for publication, February 1, 2008 , and in revised form, April 3, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant AI063432. This work was also supported by European Community 5^th Framework Programme Grant QLK2-2000-01761 (to M. N.). 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 Figs. S1–S3, Table S1, and references.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed: Dept. of Microbiology, University of Alabama at Birmingham, 613 Bevill Biomedical Research Bldg., 845 19th St. S., Birmingham, AL 35294. Tel.: 205-996-2711; Fax: 205-934-9256; E-mail: mnieder{at}uab.edu.

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