T4 AsiA blocks DNA recognition by remodeling sigma70 region 4.
Bacteriophage T4 AsiA is a versatile transcription factor capable of inhibiting host gene expression as an 'anti-sigma' factor while simultaneously promoting gene-specific expression of T4 middle genes in conjunction with T4 MotA. To accomplish this task, AsiA engages conserved region 4 of Eschericia coli sigma70, blocking recognition of most host promoters by sequestering the DNA-binding surface at the AsiA/sigma70 interface. The three-dimensional structure of an AsiA/region 4 complex reveals that the C-terminal alpha helix of region 4 is unstructured, while four other helices adopt a completely different conformation relative to the canonical structure of unbound region 4. That AsiA induces, rather than merely stabilizes, this rearrangement can be realized by comparison to the homologous structures of region 4 solved in a variety of contexts, including the structure of Thermotoga maritima sigmaA region 4 described herein. AsiA simultaneously occupies the surface of region 4 that ordinarily contacts core RNA polymerase (RNAP), suggesting that an AsiA-bound sigma70 may also undergo conformational changes in the context of the RNAP holoenzyme.
Lambert
Lester J
LJ
Laboratory of Molecular Biophysics, Rockefeller University, New York, NY 10021, USA.
Wei
Yufeng
Y
Schirf
Virgil
V
Demeler
Borries
B
Werner
Milton H
MH
D000595:Amino Acid Sequence; D004269:DNA, Bacterial / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012808:Sigma Factor / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D014764:Viral Proteins / Q000378:metabolism*
C078876:AsiA protein, Enterobacteria phage T4; D004269:DNA, Bacterial; D012808:Sigma Factor; D014764:Viral Proteins; C081775:RNA polymerase sigma 70; D012321:DNA-Directed RNA Polymerases