|Synonyms: BirA, BirA-bio-5'-AMP|
The biotin repressor, BirA, coordinately represses transcription of the divergent genes that are necessary for the synthesis of biotin |CITS:|. BirA is a bifunctional protein that possesses both regulatory and enzymatic activities: it acts as the DNA-binding transcriptional repressor of the biotin operon and also exhibits biotin ligase activity |CITS:|.
The specific inducer for BirA is biotinyl-5'-adenylate (bio-5'-AMP). In the presence of bio-5'-AMP, BirA binds to 40-nucleotide-long DNA target sites in the bioA/bioBFCD intergenic region to coordinately repress transcription of bioAp and bioBp |CITS:|. BirA-bio-5'-AMP has been observed to be predominantly monomeric in solution |CITS:|, whereas more recent studies indicate that dimerization occurs before DNA binding |CITS:|. Biotinyl-5'-adenylate |CITS:| and biotin |CITS:| stimulate dimerization and DNA binding.
The effector bio-5'-AMP is also a substrate in the BirA-mediated biotinylation of the biotin carboxyl carrier protein monomer (apoBCCP), and this relationship results in repression of the biotin operon when the abundance of apoBCCP (and therefore the cellular demand for biotin) is reduced |CITS:|. This repression is controlled by the rate of the competing protein:protein interaction. The rate of heterodimerization with apoBCCP controls the holoBirA monomer supply, and the equilibrium constant of homodimerization tunes the bioO occupancy and, consequently, transcription initiation at the biotin operon |CITS: |.
The crystal structure of BirA has been determined by X-ray crystallography to a resolution of 2.3 Å |CITS:|, and that of a BirA-biotin complex |CITS:| has been solved by several research groups.
Crystallization has been described |CITS:|, and the implications of the structure with respect to the binding of biotin and ATP have been discussed |CITS:|.Read more >
The BirA monomer contains three domains: an amino-terminal domain that contains a helix-turn-helix DNA-binding motif; the central domain, which is important for DNA binding and catalysis and contains the binding site for bio-5'-AMP; and the C-terminal domain, the funtion of which has yet to be determinded. Disordered loop structures on the protein surface appear to be involved in binding to biotin, bio-5'-AMP, and/or DNA |CITS:| and in protein dimerization |CITS:|. A model of binding and reaction progression is presented elsewhere |CITS:|.
|Sensing class:||Using internal synthesized signals|
|Connectivity class:||Local Regulator|
|Length:||966 bp / 321 aa|
|TU(s) encoding the TF:||
|Regulated gene(s)||bioA, bioB, bioC, bioD, bioF|
|Multifun term(s) of regulated gene(s)||
bioA, bioB, bioC, bioD, bioF
|Regulated operon(s)||bioA, bioBFCD|
|First gene in the operon(s)||bioA, bioB|
|Simple and complex regulons|
|Simple and complex regulatory phrases||
Regulatory phrase (List of promoters regulated by the phrase)
|Functional conformation||Function||Promoter||Sigma factor||Central Rel-Pos||Distance to first Gene||Genes||Sequence||LeftPos||RightPos||Evidence (Confirmed, Strong, Weak)||References|
|809262||809301||[SM]||, , |
|BirA-bio-5'-AMP||repressor||bioBp||Sigma70||-20.5||-62.5||bioB, bioF, bioC, bioD||
|809262||809301||[SM]||, , |
|Evolutionary conservation of regulatory elements|
 Weaver LH., Kwon K., Beckett D., Matthews BW., 2001, Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator., Proc Natl Acad Sci U S A. 98(11):6045-50
 Wilson KP., Shewchuk LM., Brennan RG., Otsuka AJ., Matthews BW., 1992, Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains., Proc Natl Acad Sci U S A. 89(19):9257-61