Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)

Nat Commun. 2013;4:1477. doi: 10.1038/ncomms2470.

Abstract

Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to the elongation factor EF-G. Here, we present an atomic model of the Tet(O)-bound 70S ribosome based on our cryo-electron microscopic reconstruction at 9.6-Å resolution. This atomic model allowed us to identify the Tet(O)-ribosome binding sites, which involve three characteristic loops in domain 4 of Tet(O). Replacements of the three amino-acid tips of these loops by a single glycine residue result in loss of Tet(O)-mediated tetracycline resistance. On the basis of these findings, the mechanism of Tet(O)-mediated tetracycline resistance can be explained in molecular detail.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / ultrastructure
  • Campylobacter jejuni / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Carrier Proteins / ultrastructure
  • Cryoelectron Microscopy
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA, Transfer / chemistry
  • RNA, Transfer / metabolism
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism*
  • Ribosome Subunits, Large, Bacterial / metabolism
  • Ribosome Subunits, Large, Bacterial / ultrastructure
  • Ribosome Subunits, Small, Bacterial / metabolism
  • Ribosome Subunits, Small, Bacterial / ultrastructure
  • Ribosomes / metabolism
  • Ribosomes / ultrastructure
  • Structural Homology, Protein
  • Tetracycline Resistance*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • GDPNP compound
  • Mutant Proteins
  • Ribosomal Proteins
  • Tet O resistance protein, Bacteria
  • Guanosine Triphosphate
  • RNA, Transfer