T4 AsiA blocks DNA recognition by remodeling σ⁷⁰ region 4

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 σ^A 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.