title: The 40-residue insertion in Vibrio cholerae FadR facilitates binding of an additional fatty acyl-CoA ligand.
abstract: FadR is a master regulator of fatty acid metabolism and influences virulence in certain members of Vibrionaceae. Among FadR homologues of the GntR family, the Vibrionaceae protein is unusual in that it contains a C-terminal 40-residue insertion. Here we report the structure of Vibrio cholerae FadR (VcFadR) alone, bound to DNA, and in the presence of a ligand, oleoyl-CoA. Whereas Escherichia coli FadR (EcFadR) contains only one acyl-CoA-binding site in each monomer, crystallographic and calorimetric data indicate that VcFadR has two. One of the binding sites resembles that of EcFadR, whereas the other, comprised residues from the insertion, has not previously been observed. Upon ligand binding, VcFadR undergoes a dramatic conformational change that would more fully disrupt DNA binding than EcFadR. These findings suggest that the ability to bind and respond to an additional ligand allows FadR from Vibrionaceae to function as a more efficient regulator.
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kovacikova
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Taylor
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Skorupski
authors.affiliation: 1] Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA [2] Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA.
authors.forename: F Jon
authors.initials: FJ
authors.lastname: Kull
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D017931:DNA Primers; C057119:FadR protein, Bacteria; D008024:Ligands; D012097:Repressor Proteins; D004247:DNA; D001616:beta-Galactosidase