Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein.
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.
Chen
Jeffrey M
JM
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Ren
Huiping
H
Shaw
James E
JE
Wang
Yu Jing
YJ
Li
Ming
M
Leung
Andrea S
AS
Tran
Vanessa
V
Berbenetz
Nicolas M
NM
Kocíncová
Dana
D
Yip
Christopher M
CM
Reyrat
Jean-Marc
JM
Liu
Jun
J
D020856:AT Rich Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004270:DNA, Circular / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004270:DNA, Circular; D004268:DNA-Binding Proteins