Cryo-EM Structure of Porphyromonas gingivalis RNA Polymerase.

[Display omitted] • First P. gingivalis RNAP structure at 3.5 Å resolution revealed new features. • P. gingivalis RNAP obtained is active and physiologically relevant. • The new orientation of its RNAP SI2 is ∼90° rotated from the one in E. coli. • Inserted region in its RNAP β' shelf may influence transcription complex assembly. • α2 in P. gingivalis RNAP ω subunit is twice as long, suggesting ω-σ interaction. Porphyromonas gingivalis , an anaerobic CFB (Cytophaga , Fusobacterium , and Bacteroides) group bacterium, is the keystone pathogen of periodontitis and has been implicated in various systemic diseases. Increased antibiotic resistance and lack of effective antibiotics necessitate a search for new intervention strategies. Here we report a 3.5 Å resolution cryo-EM structure of P. gingivalis RNA polymerase (RNAP). The structure displays new structural features in its ω subunit and multiple domains in β and β' subunits, which differ from their counterparts in other bacterial RNAPs. Superimpositions with E. coli RNAP holoenzyme and initiation complex further suggest that its ω subunit may contact the σ4 domain, thereby possibly contributing to the assembly and stabilization of initiation complexes. In addition to revealing the unique features of P. gingivalis RNAP, our work offers a framework for future studies of transcription regulation in this important pathogen, as well as for structure-based drug development. [ABSTRACT FROM AUTHOR]