title: The structural basis of signal transduction for the response regulator PrrA from Mycobacterium tuberculosis.
abstract: The structure of the two-domain response regulator PrrA from Mycobacterium tuberculosis shows a compact structure in the crystal with a well defined interdomain interface. The interface, which does not include the interdomain linker, makes the recognition helix and the trans-activation loop of the effector domain inaccessible for interaction with DNA. Part of the interface involves hydrogen-bonding interactions of a tyrosine residue in the receiver domain that is believed to be involved in signal transduction, which, if disrupted, would destabilize the interdomain interface, allowing a more extended conformation of the molecule, which would in turn allow access to the recognition helix. In solution, there is evidence for an equilibrium between compact and extended forms of the protein that is far toward the compact form when the protein is inactivated but moves toward a more extended form when activated by the cognate sensor kinase PrrB.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Nowak
authors.forename: Santosh
authors.initials: S
authors.lastname: Panjikar
authors.forename: Peter
authors.initials: P
authors.lastname: Konarev
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tucker
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D000071677:Histidine Kinase; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D012995:Solubility; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology; D014443:Tyrosine / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D015534:Trans-Activators; D014443:Tyrosine; D004247:DNA; D011494:Protein Kinases; D000071677:Histidine Kinase