Localization of the ribosomal protection protein Tet(O) on the ribosome and the mechanism of tetracycline resistance.
Tet(O) belongs to a class of ribosomal protection proteins that mediate tetracycline resistance. It is a G protein that shows significant sequence similarity to elongation factor EF-G. Here we present a cryo-electron microscopic reconstruction, at 16 A resolution, of its complex with the E. coli 70S ribosome. Tet(O) was bound in the presence of a noncleavable GTP analog to programmed ribosomal complexes carrying fMet-tRNA in the P site. Tet(O) is directly visible as a mass close to the A-site region, similar in shape and binding position to EF-G. However, there are important differences. One of them is the different location of the tip of domain IV, which in the Tet(O) case, does not overlap with the ribosomal A site but is directly adjacent to the primary tetracycline binding site. Our findings give insights into the mechanism of tetracycline resistance.
Spahn
C M
CM
Howard Hughes Medical Institute, Health Research Inc. at the Wadsworth Center, Empire State Plaza, Albany, NY 12201, USA.
Blaha
G
G
Agrawal
R K
RK
Penczek
P
P
Grassucci
R A
RA
Trieber
C A
CA
Connell
S R
SR
Taylor
D E
DE
Nierhaus
K H
KH
Frank
J
J
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002352:Carrier Proteins; D020285:Cryoelectron Microscopy; D004926:Escherichia coli / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D014176:Protein Biosynthesis / Q000187:drug effects; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D013753:Tetracycline Resistance / Q000502:physiology*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D016601:RNA-Binding Proteins; C083139:Tet O resistance protein, Bacteria