1. Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P.
- Author
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Schumacher MA, Allen GS, Diel M, Seidel G, Hillen W, and Brennan RG
- Subjects
- Allosteric Regulation genetics, Amino Acid Motifs, Amino Acid Sequence physiology, Bacillus megaterium genetics, Bacterial Proteins chemistry, Bacterial Proteins genetics, DNA chemistry, DNA genetics, DNA-Binding Proteins chemistry, DNA-Binding Proteins genetics, Histidine metabolism, Models, Molecular, Molecular Sequence Data, Molecular Structure, Phosphoprotein Phosphatases chemistry, Phosphoprotein Phosphatases genetics, Protein Binding physiology, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Protein Structure, Tertiary physiology, Repressor Proteins chemistry, Repressor Proteins genetics, Serine metabolism, Threonine metabolism, Transcription Factors chemistry, Transcription Factors genetics, Bacillus megaterium metabolism, Bacterial Proteins metabolism, DNA metabolism, DNA-Binding Proteins metabolism, Phosphoprotein Phosphatases metabolism, Repressor Proteins metabolism, Transcription Factors metabolism
- Abstract
Carbon catabolite repression (CCR) is one of the most fundamental environmental-sensing mechanisms in bacteria and imparts competitive advantage by establishing priorities in carbon metabolism. In gram-positive bacteria, the master transcription regulator of CCR is CcpA. CcpA is a LacI-GalR family member that employs, as an allosteric corepressor, the phosphoprotein HPr-Ser46-P, which is formed in glucose-replete conditions. Here we report structures of the Bacillus megaterium apoCcpA and a CcpA-(HPr-Ser46-P)-DNA complex. These structures reveal that HPr-Ser46-P mediates a novel two-component allosteric DNA binding activation mechanism that involves both rotation of the CcpA subdomains and relocation of pivot-point residue Thr61, which leads to juxtaposition of the DNA binding regions permitting "hinge" helix formation in the presence of cognate DNA. The structure of the CcpA-(HPr-Ser46-P)-cre complex also reveals the elegant mechanism by which CcpA family-specific interactions with HPr-Ser46-P residues Ser46-P and His15 partition the high-energy CCR and low-energy PTS pathways, the latter requiring HPr-His15-P.
- Published
- 2004
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