title: Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator.
abstract: Certain bacteria are able to conserve energy via the reductive dehalogenation of halo-organic compounds in a respiration-type metabolism. The transcriptional regulator CprK from Desulfitobacterium spp. induces expression of halorespiratory genes upon binding of o-chlorophenol ligands and is reversibly inactivated by oxygen through disulphide bond formation. We report crystal structures of D. hafniense CprK in the ligand-free (both oxidation states), ligand-bound (reduced) and DNA-bound states, making it the first member of the widespread CRP-FNR superfamily for which a complete structural description of both redox-dependent and allosteric molecular rearrangements is available. In conjunction with kinetic and thermodynamic ligand binding studies, we provide a model for the allosteric mechanisms underpinning transcriptional control. Amino acids that play a key role in this mechanism are not conserved in functionally distinct CRP-FNR members. This suggests that, despite significant structural homology, distinct allosteric mechanisms are used, enabling this protein family to control a very wide range of processes.
authors: Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7DN, UK.
authors: Colin
authors: C
authors: Levy
authors: Katharine
authors: K
authors: Pike
authors: Derren J
authors: DJ
authors: Heyes
authors: M Gordon
authors: MG
authors: Joyce
authors: Krisztina
authors: K
authors: Gabor
authors: Hauke
authors: H
authors: Smidt
authors: John
authors: J
authors: van der Oost
authors: David
authors: D
authors: Leys
mesh_terms: D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045858:Desulfitobacterium / Q000737:chemistry* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D054879:Halogenation; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D010084:Oxidation-Reduction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; D004268:DNA-Binding Proteins; D007506:Iron-Sulfur Proteins; D008024:Ligands