7nwg
Mammalian pre-termination 80S ribosome with Hybrid P/E- and A/P-site tRNA's bound by Blasticidin S.
Structural highlights
FunctionRSSA_RABIT Required for the assembly and/or stability of the 40S ribosomal subunit (PubMed:23873042, PubMed:25601755). Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits (PubMed:23873042, PubMed:25601755). Also functions as a cell surface receptor for laminin (By similarity). Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways (By similarity). May play a role in cell fate determination and tissue morphogenesis (By similarity). Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria. Acts as a PPP1R16B-dependent substrate of PPP1CA (By similarity).[HAMAP-Rule:MF_03016][1] [2] Publication Abstract from PubMedDeciphering 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. Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA.,Powers KT, Stevenson-Jones F, Yadav SKN, Amthor B, Bufton JC, Borucu U, Shen D, Becker JP, Lavysh D, Hentze MW, Kulozik AE, Neu-Yilik G, Schaffitzel C Nucleic Acids Res. 2021 Jul 21;49(13):7665-7679. doi: 10.1093/nar/gkab532. PMID:34157102[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
