title: A Pseudomonas aeruginosa transcription factor that senses fatty acid structure.
abstract: Cells regulate their membrane phospholipid biophysical properties by the co-ordinated synthesis of saturated and unsaturated fatty acids. In bacteria, unsaturated fatty acids are produced by the de novo fatty acid biosynthetic pathway anaerobically, or by oxidative desaturation of the existing fatty acids catalysed by desaturases. A transcriptional repressor in Pseudomonas aeruginosa, DesT (PA4890), regulates the expression of an acyl-CoA desaturase operon (desCB, PA4889 and PA4888). The desCB operon is located adjacent to desT and is transcribed in the opposite direction. The expression level of desCB is strongly and selectively upregulated in a DeltadesT-deletion strain. Both electrophoresis mobility shift assay and DNase I footprinting analysis demonstrated the existence of two DesT binding sites in the desT-desCB promoter region, P1 and P2. The binding of purified DesT to P2 was enhanced by unsaturated acyl-CoAs, whereas saturated acyl-CoAs prevented DesT interaction with P2. The biological importance of this interaction was verified by the upregulation of desCB and desT in cells grown in the presence of stearate and their repression when oleate was present. This unique ligand selectivity allows DesT to sense the physical properties of the cellular acyl-CoA pool and modulate the expression of the acyl-CoA Delta9-desaturase system to adjust fatty acid desaturation activity accordingly.
authors: Protein Science Division, Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA. zhang@stjude.org
authors: Yong-Mei
authors: YM
authors: Zhang
authors: Kun
authors: K
authors: Zhu
authors: Matthew W
authors: MW
authors: Frank
authors: Charles O
authors: CO
authors: Rock
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D005227:Fatty Acids; D011994:Recombinant Proteins; D014157:Transcription Factors; D003850:Deoxyribonuclease I