| Structural highlights
Function
RSSA_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 PubMed
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.
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 Also
References
- ↑ Lomakin IB, Steitz TA. The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature. 2013 Jul 21. doi: 10.1038/nature12355. PMID:23873042 doi:10.1038/nature12355
- ↑ Muhs M, Hilal T, Mielke T, Skabkin MA, Sanbonmatsu KY, Pestova TV, Spahn CM. Cryo-EM of Ribosomal 80S Complexes with Termination Factors Reveals the Translocated Cricket Paralysis Virus IRES. Mol Cell. 2015 Feb 5;57(3):422-432. doi: 10.1016/j.molcel.2014.12.016. Epub 2015 , Jan 15. PMID:25601755 doi:http://dx.doi.org/10.1016/j.molcel.2014.12.016
- ↑ 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. Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA. Nucleic Acids Res. 2021 Jul 21;49(13):7665-7679. doi: 10.1093/nar/gkab532. PMID:34157102 doi:http://dx.doi.org/10.1093/nar/gkab532
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