{Reference Type}: Journal Article
{Title}: Protein:protein interactions in control of a transcriptional switch.
{Author}: Adikaram PR;Beckett D;
{Journal}: J Mol Biol
{Volume}: 425
{Issue}: 22
{Year}: Nov 2013 15
{Factor}: 6.151
{DOI}: 10.1016/j.jmb.2013.07.029
{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.