Structural highlights
Function
CCPA_BACSU Global transcriptional regulator of carbon catabolite repression (CCR) and carbon catabolite activation (CCA), which ensures optimal energy usage under diverse conditions. Interacts with either P-Ser-HPr or P-Ser-Crh, leading to the formation of a complex that binds to DNA at the catabolite-response elements (cre). Binding to DNA allows activation or repression of many different genes and operons.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
In Gram-positive bacteria, the catabolite control protein A (CcpA) functions as the master transcriptional regulator of carbon catabolite repression/regulation (CCR). To effect CCR, CcpA binds a phosphoprotein, either HPr-Ser46-P or Crh-Ser46-P. Although Crh and histidine-containing protein (HPr) are structurally homologous, CcpA binds Crh-Ser46-P more weakly than HPr-Ser46-P. Moreover, Crh can form domain-swapped dimers, which have been hypothesized to be functionally relevant in CCR. To understand the molecular mechanism of Crh-Ser46-P regulation of CCR, we determined the structure of a CcpA-(Crh-Ser46-P)-DNA complex. The structure reveals that Crh-Ser46-P does not bind CcpA as a dimer but rather interacts with CcpA as a monomer in a manner similar to that of HPr-Ser46-P. The reduced affinity of Crh-Ser46-P for CcpA as compared with that of HPr-Ser46 P is explained by weaker Crh-Ser46-P interactions in its contact region I to CcpA, which causes this region to shift away from CcpA. Nonetheless, the interface between CcpA and helix alpha 2 of the second contact region (contact region II) of Crh-Ser46-P is maintained. This latter finding demonstrates that this contact region is necessary and sufficient to throw the allosteric switch to activate cre binding by CcpA.
Phosphoprotein Crh-Ser46-P displays altered binding to CcpA to effect carbon catabolite regulation.,Schumacher MA, Seidel G, Hillen W, Brennan RG J Biol Chem. 2006 Mar 10;281(10):6793-800. Epub 2005 Nov 29. PMID:16316990[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Henkin TM, Grundy FJ, Nicholson WL, Chambliss GH. Catabolite repression of alpha-amylase gene expression in Bacillus subtilis involves a trans-acting gene product homologous to the Escherichia coli lacl and galR repressors. Mol Microbiol. 1991 Mar;5(3):575-84. PMID:1904524
- ↑ Kim JH, Guvener ZT, Cho JY, Chung KC, Chambliss GH. Specificity of DNA binding activity of the Bacillus subtilis catabolite control protein CcpA. J Bacteriol. 1995 Sep;177(17):5129-34. PMID:7665492
- ↑ Tobisch S, Zuhlke D, Bernhardt J, Stulke J, Hecker M. Role of CcpA in regulation of the central pathways of carbon catabolism in Bacillus subtilis. J Bacteriol. 1999 Nov;181(22):6996-7004. PMID:10559165
- ↑ Ludwig H, Stulke J. The Bacillus subtilis catabolite control protein CcpA exerts all its regulatory functions by DNA-binding. FEMS Microbiol Lett. 2001 Sep 11;203(1):125-9. PMID:11557150
- ↑ Schumacher MA, Sprehe M, Bartholomae M, Hillen W, Brennan RG. Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators. Nucleic Acids Res. 2010 Nov 23. PMID:21106498 doi:10.1093/nar/gkq1177
- ↑ Schumacher MA, Seidel G, Hillen W, Brennan RG. Phosphoprotein Crh-Ser46-P displays altered binding to CcpA to effect carbon catabolite regulation. J Biol Chem. 2006 Mar 10;281(10):6793-800. Epub 2005 Nov 29. PMID:16316990 doi:10.1074/jbc.M509977200
