Nucleic Acids Research Advance Access published online on January 10, 2008
Nucleic Acids Research, doi:10.1093/nar/gkm1162
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Molecular Biology |
Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein
1Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, 2Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 3G9, Canada, 3Université Paris Descartes, Faculté de Médecine René Descartes and 4Inserm, U570, Unité de Pathogénie des Infections Systémiques-Groupe AVENIR, Paris Cedex 15, F-75730, France
*To whom correspondence should be addressed: Tel: 416 946 5067; Fax: 416 978 6885; Email: jun.liu{at}utoronto.ca
Received November 22, 2007. Revised December 12, 2007. Accepted December 13, 2007.
Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Recent studies suggest that Lsr2 is a regulatory protein involved in multiple cellular processes including cell wall biosynthesis and antibiotic resistance. However, the underlying molecular mechanisms remain unknown. In this article, we performed biochemical studies of Lsr2–DNA interactions and structure–function analysis of Lsr2. Analysis by atomic force microscopy revealed that Lsr2 has the ability to bridge distant DNA segments, suggesting that Lsr2 plays a role in the overall organization and compactness of the nucleoid. Mutational analysis identified critical residues and selection of dominant negative mutants demonstrated that both DNA binding and protein oligomerization are essential for the normal functions of Lsr2 in vivo. These results provide strong evidence that Lsr2 is a DNA bridging protein, which represents the first identification of such proteins in bacteria phylogenetically distant from the Enterobacteriaceae. DNA bridging by Lsr2 also provides a mechanism of transcriptional regulation by Lsr2.
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