title: Flipping a genetic switch by subunit exchange.
abstract: 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 sigma(70), 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-sigma(70) complex reveals that these interfaces are coincident. Thus, the AsiA interaction with sigma(70) 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.
authors.affiliation: Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, Box 42, New York, NY 10021, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Lambert
authors.forename: V
authors.initials: V
authors.lastname: Schirf
authors.forename: B
authors.initials: B
authors.lastname: Demeler
authors.forename: M
authors.initials: M
authors.lastname: Cadene
authors.forename: M H
authors.initials: MH
authors.lastname: Werner
mesh_terms: D017122:Bacteriophage T4 / Q000378:metabolism*; D019281:Dimerization; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C078876:AsiA protein, Enterobacteria phage T4; D014764:Viral Proteins