Abstract
Catabolite control protein C (CcpC) belongs to the LysR-type transcriptional regulator (LTTR) family, which regulates the transcription of genes encoding the tricarboxylic acid branch enzymes of the TCA cycle by responding to a pathway-specific metabolite, citrate. The biological function of CcpC has been characterized several times, but the structural basis for the molecular function of CcpC remains elusive. Here, we report the characterization of a full-length CcpC from Bacillus amyloliquefaciens (BaCcpC-FL) and a crystal structure of the C-terminal inducer-binding domain (IBD) complexed with citrate. BaCcpC required both dyad symmetric regions I and II to recognize the citB promoter, and the presence of citrate reduced citB promoter binding. The crystal structure of CcpC-IBD shows two subdomains, IBD-I and IBD-II, and a citrate molecule buried between them. Ile100, two arginines (Arg147 and Arg260), and three serines (Ser129, Ser189, and Ser191) exhibit strong hydrogen-bond interactions with citrate molecules. A structural comparison of BaCcpC-IBD with its homologues showed that they share the same tail-to-tail dimer alignment, but the dimeric interface and the rotation between these molecules exhibit significant differences. Taken together, our results provide a framework for understanding the mechanism underlying the functional divergence of the CcpC protein.
Highlights
The tricarboxylic acid (TCA) cycle, known as the Krebs cycle or the citric acid cycle (CAC), is a central metabolic pathway in the cell[1]
In B. subtilis, Catabolite control protein C (CcpC) binds to two sites within the citB promoter region, a dyad symmetry element centred at position −66 that induces of the transcriptional start site and a half-dyad element located at position −27 to −3326
The crystal structure of BaCcpC-inducer-binding domain (IBD) was compared with structures of the LysR-type transcriptional regulator (LTTR) family members
Summary
The tricarboxylic acid (TCA) cycle, known as the Krebs cycle or the citric acid cycle (CAC), is a central metabolic pathway in the cell[1]. In the B. amyloliquefaciens genome, the potential promoter region of citB (named citB-P) was found from position −73 to −20, and it shows high similarity with the same DNA-binding boxes “ATAA”, “TTAT”, and “TATT” (Fig. 1A). This result indicates that BaCcpC has a high binding affinity for citB promoter DNA of B. amyloliquefaciens.
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