T4 AsiA blocks DNA recognition by remodeling σ70 region 4

Lester J. Lambert, Yufeng Wei, Virgil Schirf, Borries Demeler, Milton H. Werner

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Bacteriophage T4 AsiA is a versatile transcription factor capable of inhibiting host gene expression as an 'anti-σ' 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 σ70, blocking recognition of most host promoters by sequestering the DNA-binding surface at the AsiA/σ70 interface. The three-dimensional structure of an AsiA/region 4 complex reveals that the C-terminal α 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 σA region 4 described herein. AsiA simultaneously occupies the surface of region 4 that ordinarily contacts core RNA polymerase (RNAP), suggesting that an AsiA-bound σ70 may also undergo conformational changes in the context of the RNAP holoenzyme.

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Keywords

  • AsiA
  • NMR
  • RNA polymerase
  • Sigma70
  • Structure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Lambert, L. J., Wei, Y., Schirf, V., Demeler, B., & Werner, M. H. (2004). T4 AsiA blocks DNA recognition by remodeling σ70 region 4. EMBO Journal, 23(15), 2952-2962. https://doi.org/10.1038/sj.emboj.7600312