Promoter-Specific Transcription Inhibition in Staphylococcus aureus by a Phage Protein

Phage G1 gp67 is a 23 kDa protein that binds to the Staphylococcus aureus (Sau) RNA polymerase (RNAP) sigma(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-angstrom-resolution crystal structure of the complex between gp67 and Sau sigma(A) domain 4 (sigma(A)(4)) explains how gp67 joins the RNAP promoter complex through sigma(A)(4) without significantly affecting sigma(A)(4) function. Our results indicate that gp67 forms a complex with RNAP at most, if not all, sigma(A)-dependent promoters, but selectively inhibits promoters that depend on an interaction between upstream DNA and the RNAP alpha-subunit C-terminal domain (alpha CTD). Thus, we reveal a promoter-specific transcription inhibition mechanism by which gp67 interacts with the RNAP promoter complex through one subunit (sigma(A)), and selectively affects the function of another subunit (alpha CTD) depending on promoter usage.