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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Allosteric Regulation / genetics
-
Amino Acid Motifs
-
Amino Acid Sequence / physiology
-
Bacillus megaterium / genetics
-
Bacillus megaterium / metabolism*
-
Bacterial Proteins / chemistry
-
Bacterial Proteins / genetics
-
Bacterial Proteins / metabolism*
-
DNA / chemistry
-
DNA / genetics
-
DNA / metabolism*
-
DNA-Binding Proteins / chemistry
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Histidine / metabolism
-
Models, Molecular
-
Molecular Sequence Data
-
Molecular Structure
-
Phosphoprotein Phosphatases / chemistry
-
Phosphoprotein Phosphatases / genetics
-
Phosphoprotein Phosphatases / metabolism*
-
Protein Binding / physiology
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism
-
Protein Structure, Tertiary / physiology
-
Repressor Proteins / chemistry
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism*
-
Serine / metabolism
-
Threonine / metabolism
-
Transcription Factors / chemistry
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
Substances
-
Bacterial Proteins
-
DNA-Binding Proteins
-
Repressor Proteins
-
Transcription Factors
-
catabolite control proteins, bacteria
-
Threonine
-
Serine
-
Histidine
-
DNA
-
HPr kinase
-
Protein Serine-Threonine Kinases
-
Phosphoprotein Phosphatases
Associated data
-
PDB/1RZR
-
PDB/1SXG
-
PDB/1SXH
-
PDB/1SXI