Structures of Mycobacterium tuberculosis DosR and DosR-DNA complex involved in gene activation during adaptation to hypoxic latency.
On encountering low oxygen conditions, DosR activates the transcription of 47 genes, promoting long-term survival of Mycobacterium tuberculosis in a non-replicating state. Here, we report the crystal structures of the DosR C-terminal domain and its complex with a consensus DNA sequence of the hypoxia-induced gene promoter. The DosR C-terminal domain contains four alpha-helices and forms tetramers consisting of two dimers with non-intersecting dyads. In the DNA-bound structure, each DosR C-terminal domain in a dimer places its DNA-binding helix deep into the major groove, causing two bends in the DNA. DosR makes numerous protein-DNA base contacts using only three amino acid residues per subunit: Lys179, Lys182, and Asn183. The DosR tetramer is unique among response regulators with known structures.
Wisedchaisri
Goragot
G
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Wu
Meiting
M
Rice
Adrian E
AE
Roberts
David M
DM
Sherman
David R
DR
Hol
Wim G J
WG
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism / Q000382:microbiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009690:Nucleic Acid Conformation; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D015533:Transcriptional Activation
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010100:Oxygen