Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

Nat Commun. 2017 Jul 13:8:16072. doi: 10.1038/ncomms16072.

Abstract

The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • DNA-Directed RNA Polymerases / metabolism*
  • Molecular Structure
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism
  • Mycobacterium smegmatis / chemistry*
  • Mycobacterium smegmatis / enzymology
  • Mycobacterium smegmatis / genetics
  • Promoter Regions, Genetic*
  • Transcription Initiation Site
  • Transcription, Genetic*

Substances

  • Multiprotein Complexes
  • DNA-Directed RNA Polymerases