4V9C

Allosteric control of the ribosome by small-molecule antibiotics

This is a non-PDB format compatible entry.

Summary for 4V9C

• Entry DOI: 10.2210/pdb4v9c/pdb
• Descriptor: 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (59 entities in total)
• Functional Keywords: nucleic acid conformation, protein biosynthesis, antibiotic, neomycin, aminoglycoside, rrf, recycling, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm:
• Total number of polymer chains: 109
• Total formula weight: 4402452.12

Authors

Cate, J.H.D.,Pulk, A.,Blanchard, S.C.,Wang, L.,Feldman, M.B.,Wasserman, M.R.,Altman, R. (deposition date: 2012-07-25, release date: 2014-07-09, Last modification date: 2024-10-30)

Primary citation

Wang, L.,Pulk, A.,Wasserman, M.R.,Feldman, M.B.,Altman, R.B.,Doudna Cate, J.H.,Blanchard, S.C.
Allosteric control of the ribosome by small-molecule antibiotics.
Nat.Struct.Mol.Biol., 19:957-963, 2012

PubMed 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.

PubMed: 22902368
DOI: 10.1038/nsmb.2360

Experimental method

X-RAY DIFFRACTION (3.3 Å)