Flipping a genetic switch by subunit exchange

Lester J. Lambert, Virgil Schirf, Borries Demeler, Martine Cadene, Milton H. Werner

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The bacteriophage T4 AsiA protein is a multifunctional protein that simultaneously acts as both a repressor and activator of gene expression during the phage life cycle. These dual roles with opposing transcriptional consequences are achieved by modification of the host RNA polymerase in which AsiA binds to conserved region 4 (SR4) of σ70, altering the pathway of promoter selection by the holoenzyme. The mechanism by which AsiA flips this genetic switch has now been revealed, in part, from the three-dimensional structure of AsiA and the elucidation of its interaction with SR4. The structure of Asia is that of a novel homodimer in which each monomer is constructed as a seven-helix bundle arranged in four overlapping helix-loop-helix elements. Identification of the protein interfaces for both the AsiA homodimer and the AsiA-σ70 complex reveals that these interfaces are coincident. Thus, the AsiA interaction with σ70 necessitates that the Asia homodimer dissociate to form an AsiA-SR4 heterodimer, exchanging one protein subunit for another to alter promoter choice by RNA polymerase.

Original languageEnglish
Pages (from-to)7149-7159
Number of pages11
JournalEMBO Journal
Issue number24
StatePublished - Dec 17 2001


  • AsiA
  • NMR
  • Subunit exchange
  • Three- dimensional structure
  • σ


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