3C3W

Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR

Summary for 3C3W

• Entry DOI: 10.2210/pdb3c3w/pdb
• Related: 1zlj 1zlk
• Descriptor: TWO COMPONENT TRANSCRIPTIONAL REGULATORY PROTEIN DEVR, SULFATE ION (3 entities in total)
• Functional Keywords: response regulator, two-component regulatory system, dna-binding protein, tuberculosis, transcription, transcription regulation
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cytoplasm (Probable): P95193
• Total number of polymer chains: 2
• Total formula weight: 48888.42

Authors

Wisedchaisri, G.,Wu, M.,Sherman, D.R.,Hol, W.G.J. (deposition date: 2008-01-28, release date: 2008-04-22, Last modification date: 2024-04-03)

Primary citation

Wisedchaisri, G.,Wu, M.,Sherman, D.R.,Hol, W.G.
Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation
J.Mol.Biol., 378:227-242, 2008

PubMed Abstract: The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one-third of the world's population. Here, we report crystal structures of full-length unphosphorylated DosR at 2.2 A resolution and its C-terminal DNA-binding domain at 1.7 A resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected (beta alpha)(4) topology instead of the canonical (beta alpha)(5) fold observed in other response regulators. The linker region adopts a unique conformation that contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix alpha 10, which allows Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix alpha 10 residues, different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism.

PubMed: 18353359
DOI: 10.1016/j.jmb.2008.02.029

Experimental method

X-RAY DIFFRACTION (2.2 Å)