Poster Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Crystal structures of an unusual transcriptional activator from bacteriophage 186 (#109)

Jia Q Truong 1 , Santosh Panjikar 2 , Ian B Dodd 1 , John B Bruning 1 , Keith E Shearwin 1
  1. University of Adelaide, Adelaide, SOUTH AUSTRALIA, Australia
  2. Australian Synchrotron, Clayton, South Australia, Australia

The temperate coliphage 186, after infecting its host bacterium Escherichia coli, can follow either the lytic or the lysogenic developmental pathways. Crucial to this developmental decision is the lysogeny promoting factor CII. This potent transcriptional activator activates the early lysogenic promoter pE at least 400 fold, to build up sufficient immunity repressor levels for a portion of infections to commit to lysogeny.  Its potency and its unusual property of binding to half sites separated by 20 base pairs, center-to-center, suggests it may activate the pE promoter by a novel mechanism. Three crystal structures of the CII protein were solved to 2-3Å. The structures reveal that a tetrameric arrangement of CII is necessary for DNA binding, which was subsequently validated by mutational analysis and native mass-spectrometry. CII is degraded in vivo into a specific transcriptionally inactive product. The crystal structures explain the altered self-association of the degradation product and its loss of activity. The structures combined with mutagenesis data provide a basis for modelling the CII-RNA polymerasecomplex at the promoter to aid in understanding the promoter activation mechanism.