Promoter-specific transcription inhibition in Staphylococcus aureus by a phage protein

Summary Phage G1 gp67 is a 23 kDa protein that binds to the  Staphylococcus aureus ( Sau ) RNA polymerase (RNAP) σ A subunit and blocks cell growth by inhibiting transcription. We show that gp67 has little to no effect on transcription from most promoters but is a potent inhibitor of ribosomal RNA transcription. A 2.0-A-resolution crystal structure of the complex between gp67 and Sau σ A domain 4 (σ A 4 ) explains how gp67 joins the RNAP promoter complex through σ A 4 without significantly affecting σ A 4 function. Our results indicate that gp67 forms a complex with RNAP at most, if not all, σ A -dependent promoters, but selectively inhibits promoters that depend on an interaction between upstream DNA and the RNAP α-subunit C-terminal domain (αCTD). Thus, we reveal a promoter-specific transcription inhibition mechanism by which gp67 interacts with the RNAP promoter complex through one subunit (σ A ), and selectively affects the function of another subunit (αCTD) depending on promoter usage.