The transcription regulator RbsR represents a novel interaction partner of the phosphoprotein HPr-Ser46-P in Bacillus subtilis.
Histidine-containing protein (HPr) is a central metabolic sensor in low-GC Gram-positive bacteria and plays a dual role in sugar uptake by the phosphoenolpyruvate-sugar phosphotransferase system and in transcriptional control during carbon catabolite repression. The latter process is mediated by interaction between HPr and the carbon catabolite repression master transcription regulator, carbon catabolite protein A (CcpA), a member of the LacI-GalR family of DNA-binding proteins. We investigated, with a combination of computational and experimental tools, whether HPr can also interact with other transcriptional regulators. To allow rapid identification of paralogous LacI-GalR family members that might interact with HPr in a similar fashion to CcpA, a structure-based computational approach was developed which relies on the analysis of the similarity of protein-protein interfaces between different complexes. A key element of this method is an empirical pair potential derived from a group of orthologous complexes and subsequently used to identify paralogs that exhibit similar properties of their protein interfaces. Application of this method to the family of LacI-GalR repressors in Bacillus subtilis predicted the ribose operon repressor (RbsR) as a novel interaction partner of HPr. This interaction was subsequently confirmed experimentally and suggests that HPr plays an even larger role in transcriptional control than previously expected.
Müller
Wolfgang
W
Institut für Biochemie, Abteilung Bioinformatik, Universität Erlangen-Nürnberg, Erlangen, Germany.
Horstmann
Nicola
N
Hillen
Wolfgang
W
Sticht
Heinrich
H
D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006639:Histidine / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009876:Operon; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping / Q000379:methods*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017385:Sequence Homology; D013912:Threonine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; C442131:ScoC protein, Bacillus subtilis; D014157:Transcription Factors; D013912:Threonine; D006639:Histidine; D017346:Protein Serine-Threonine Kinases