Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis

Nucleic Acids Res. 2017 Oct 13;45(18):10884-10894. doi: 10.1093/nar/gkx785.

Abstract

Ribosomes from Mycobacterium tuberculosis (Mtb) possess species-specific ribosomal RNA (rRNA) expansion segments and ribosomal proteins (rProtein). Here, we present the near-atomic structures of the Mtb 50S ribosomal subunit and the complete Mtb 70S ribosome, solved by cryo-electron microscopy. Upon joining of the large and small ribosomal subunits, a 100-nt long expansion segment of the Mtb 23S rRNA, named H54a or the 'handle', switches interactions from with rRNA helix H68 and rProtein uL2 to with rProtein bS6, forming a new intersubunit bridge 'B9'. In Mtb 70S, bridge B9 is mostly maintained, leading to correlated motions among the handle, the L1 stalk and the small subunit in the rotated and non-rotated states. Two new protein densities were discovered near the decoding center and the peptidyl transferase center, respectively. These results provide a structural basis for studying translation in Mtb as well as developing new tuberculosis drugs.

MeSH terms

  • Cryoelectron Microscopy
  • Models, Molecular
  • Motion
  • Mycobacterium smegmatis / chemistry
  • Mycobacterium tuberculosis / chemistry*
  • Protein Synthesis Inhibitors
  • Ribosomal Proteins / chemistry
  • Ribosome Subunits, Large, Bacterial / chemistry
  • Ribosomes / chemistry*
  • Species Specificity

Substances

  • Protein Synthesis Inhibitors
  • Ribosomal Proteins