Protein:protein interactions in control of a transcriptional switch.

Article Details

Citation

Adikaram PR, Beckett D

Protein:protein interactions in control of a transcriptional switch.

J Mol Biol. 2013 Nov 15;425(22):4584-94. doi: 10.1016/j.jmb.2013.07.029. Epub 2013 Jul 26.

PubMed ID
23896299 [ View in PubMed
]
Abstract

Protein partner exchange plays a key role in regulating many biological switches. Although widespread, the mechanisms dictating protein partner identity and, therefore, the outcome of a switch have been determined for a limited number of systems. The Escherichia coli protein BirA undergoes a switch between posttranslational biotin attachment and transcription repression in response to cellular biotin demand. Moreover, the functional switch reflects formation of alternative mutually exclusive protein:protein interactions by BirA. Previous studies provided a set of alanine-substituted BirA variants with altered kinetic and equilibrium parameters of forming these interactions. In this work, DNase I footprinting measurements were employed to investigate the consequences of these altered properties for the outcome of the BirA functional switch. The results support a mechanism in which BirA availability for DNA binding and, therefore, transcription repression is controlled by the rate of the competing protein:protein interaction. However, occupancy of the transcriptional regulatory site on DNA by BirA is exquisitely tuned by the equilibrium constant governing its homodimerization.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Bifunctional ligase/repressor BirAP06709Details