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

J. Biol. Chem., Vol. 280, Issue 17, 17397-17407, April 29, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/17/17397    most recent M501128200v1 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 Lah, J. Articles by Loris, R. Search for Related Content PubMed PubMed Citation Articles by Lah, J. Articles by Loris, R. Social Bookmarking                      What's this?

Energetics of Structural Transitions of the Addiction Antitoxin MazE

IS A PROGRAMMED BACTERIAL CELL DEATH DEPENDENT ON THE INTRINSICALLY FLEXIBLE NATURE OF THE ANTITOXINS?^*

Jurij Lah, Mario imi, Gorazd Vesnaver, Irina Marianovsky¶, Gad Glaser¶, Hanna Engelberg-Kulka||, and Remy Loris**

From the University of Ljubljana, Faculty of Chemistry and Chemical Technology, Askerceva 5, 1000 Ljubljana, Slovenia, the Departments of ^¶Cellular Biochemistry and ^||Molecular Biology, Hebrew University-Hadassah Medical School, Ein Kerem, Jerusalem 91120, Israel, and the ^**Laboratorium voor Ultrastructuur, Instituut voor Moleculaire Biologie, Vrije Universiteit Brussel and Vlaams Instituut voor Biotechnologie, Pleinlaan 2, B-1050 Brussels, Belgium

The Escherichia coli mazEF addiction module plays a crucial role in the cell death program that is triggered under various stress conditions. It codes for the toxin MazF and the antitoxin MazE, which interferes with the lethal action of the toxin. To better understand the role of various conformations of MazE in bacterial life, its order-disorder transitions were monitored by differential scanning calorimetry, spectropolarimetry, and fluorimetry. The changes in spectral and thermodynamic properties accompanying MazE dimer denaturation can be described in terms of a compensating reversible process of the partial folding of the unstructured C-terminal half (high mean net charge, low mean hydrophobicity) and monomerization coupled with the partial unfolding of the structured N-terminal half (low mean net charge, high mean hydrophobicity). At pH 4.5 and T < 50 °C, the unstructured polypeptide chains of the MazE dimer fold into (pre)molten globule-like conformations that thermally stabilize the dimeric form of the protein. The simulation based on the thermodynamic and structural information on various addiction modules suggests that both the conformational adaptability of the dimeric antitoxin form (binding to the toxins and DNA) and the reversible transformation to the more flexible monomeric form are essential for the regulation of bacterial cell life and death.

Received for publication, January 31, 2005 , and in revised form, February 24, 2005.

^* This work was supported by Grant P1-0201 from the Ministry of Education, Science, and Sports of Slovenia; by the Vlaams Interuniversitair Instituut voor Biotechnologie; the Onderzoeksraad of the Vlaams Instituut voor Biotechnologie; the Fonds voor Wetenschappelijk Onderzoek Vlaanderen; and by Israel Science Foundation Grants 507/03 (to H. E.-K.) and 938/04 (to G. G.) from the Israel Academy of Science and Humanities. 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 "Experimental Procedures," supplemental Equations 1–15, and a supplemental figure.

To whom correspondence should be addressed. Tel.: 386-1-241-9414; Fax: 386-1-241-9437; E-mail: jurij.lah{at}fkkt.uni-lj.si.

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

This article has been cited by other articles:

				M. Simic, N. De Jonge, R. Loris, G. Vesnaver, and J. Lah Driving Forces of Gyrase Recognition by the Addiction Toxin CcdB J. Biol. Chem., July 24, 2009; 284(30): 20002 - 20010. [Abstract] [Full Text] [PDF]

				S. M. Simon, F. J. R. Sousa, R. Mohana-Borges, and G. C. Walker Regulation of Escherichia coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products PNAS, January 29, 2008; 105(4): 1152 - 1157. [Abstract] [Full Text] [PDF]

				E. M. Moritz and P. J. Hergenrother Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci PNAS, January 2, 2007; 104(1): 311 - 316. [Abstract] [Full Text] [PDF]

				H. Engelberg-Kulka, R. Hazan, and S. Amitai mazEF: a chromosomal toxin-antitoxin module that triggers programmed cell death in bacteria J. Cell Sci., October 1, 2005; 118(19): 4327 - 4332. [Abstract] [Full Text] [PDF]

				Y. Zhang, L. Zhu, J. Zhang, and M. Inouye Characterization of ChpBK, an mRNA Interferase from Escherichia coli J. Biol. Chem., July 15, 2005; 280(28): 26080 - 26088. [Abstract] [Full Text] [PDF]