Summary information and primary citation
- PDB-id
-
4v9c;
DSSR-derived features in text and
JSON formats; DNAproDB
- Class
- ribosome-antibiotic
- Method
- X-ray (3.3 Å)
- Summary
- Allosteric control of the ribosome by small-molecule
antibiotics
- Reference
-
Wang L, Pulk A, Wasserman MR, Feldman MB, Altman RB,
Doudna Cate JH, Blanchard SC (2012): "Allosteric
control of the ribosome by small-molecule
antibiotics." Nat.Struct.Mol.Biol.,
19, 957-963. doi: 10.1038/nsmb.2360.
- Abstract
- Protein synthesis is targeted by numerous, chemically
distinct antibiotics that bind and inhibit key functional
centers of the ribosome. Using single-molecule imaging and
X-ray crystallography, we show that the aminoglycoside
neomycin blocks aminoacyl-transfer RNA (aa-tRNA) selection
and translocation as well as ribosome recycling by binding
to helix 69 (H69) of 23S ribosomal RNA within the large
subunit of the Escherichia coli ribosome. There, neomycin
prevents the remodeling of intersubunit bridges that
normally accompanies the process of subunit rotation to
stabilize a partially rotated ribosome configuration in
which peptidyl (P)-site tRNA is constrained in a previously
unidentified hybrid position. Direct measurements show that
this neomycin-stabilized intermediate is incompatible with
the translation factor binding that is required for
distinct protein synthesis reactions. These findings reveal
the functional importance of reversible intersubunit
rotation to the translation mechanism and shed new light on
the allosteric control of ribosome functions by
small-molecule antibiotics.