title: Mechanism of tetracycline resistance by ribosomal protection protein Tet(O).
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.
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
authors: Wen
authors: W
authors: Li
authors: Gemma C
authors: GC
authors: Atkinson
authors: Nehal S
authors: NS
authors: Thakor
authors: Ular
authors: U
authors: Allas
authors: Chuao-chao
authors: CC
authors: Lu
authors: Kwok-Yan
authors: KY
authors: Chan
authors: Tanel
authors: T
authors: Tenson
authors: Klaus
authors: K
authors: Schulten
authors: Kevin S
authors: KS
authors: Wilson
authors: Vasili
authors: V
authors: Hauryliuk
authors: Joachim
authors: J
authors: Frank
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D016123:Campylobacter jejuni / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*; D054681:Ribosome Subunits, Large, Bacterial / Q000378:metabolism / Q000648:ultrastructure; D054680:Ribosome Subunits, Small, Bacterial / Q000378:metabolism / Q000648:ultrastructure; D012270:Ribosomes / Q000378:metabolism / Q000648:ultrastructure; D040681:Structural Homology, Protein; D013753:Tetracycline Resistance
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C503923:GDPNP compound; D050505:Mutant Proteins; D012269:Ribosomal Proteins; C083139:Tet O resistance protein, Bacteria; D006160:Guanosine Triphosphate; D012343:RNA, Transfer
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