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TitleBlasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA.
Journal, issue, pagesNucleic Acids Res, Vol. 49, Issue 13, Page 7665-7679, Year 2021
Publish dateJul 21, 2021
AuthorsKyle T Powers / Flint Stevenson-Jones / Sathish K N Yadav / Beate Amthor / Joshua C Bufton / Ufuk Borucu / Dakang Shen / Jonas P Becker / Daria Lavysh / Matthias W Hentze / Andreas E Kulozik / Gabriele Neu-Yilik / Christiane Schaffitzel /
PubMed AbstractDeciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding ...Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3'CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor 1 (eRF1), it interferes with eRF1's accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production.
External linksNucleic Acids Res / PubMed:34157102 / PubMed Central
MethodsEM (single particle)
Resolution3.13 - 4.1 Å
Structure data

12631

7nwg

EMDB-12631, PDB-7nwg:
Mammalian pre-termination 80S ribosome with Hybrid P/E- and A/P-site tRNA's bound by Blasticidin S.
Method: EM (single particle) / Resolution: 3.8 Å

12632

7nwh

EMDB-12632, PDB-7nwh:
Mammalian pre-termination 80S ribosome with eRF1 and eRF3 bound by Blasticidin S.
Method: EM (single particle) / Resolution: 4.1 Å

12633

7nwi

EMDB-12633, PDB-7nwi:
Mammalian pre-termination 80S ribosome with Empty-A site bound by Blasticidin S
Method: EM (single particle) / Resolution: 3.13 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-BLS:
BLASTICIDIN S / antibiotic*YM

ChemComp-ZN:
Unknown entry

ChemComp-GCP:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-PCP, energy-carrying molecule analogue*YM

Source
  • oryctolagus cuniculus (rabbit)
  • Rabbit (rabbit)
KeywordsRIBOSOME / Inhibitor 80S Termination Complex Blasticidin S Translation NMD

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