5h5u
Mechanistic insights into the alternative translation termination by ArfA and RF2
Structural highlights
FunctionRL6_ECOLI This protein binds directly to at least 2 domains of the 23S ribosomal RNA, thus is important in its secondary structure. It is located near the subunit interface in the base of the L7/L12 stalk, and near the tRNA binding site of the peptidyltransferase center.[HAMAP-Rule:MF_01365] Gentamicin-resistant mutations in this protein affect translation fidelity.[HAMAP-Rule:MF_01365] Publication Abstract from PubMedDuring cellular translation of mRNAs by ribosomes, various situations that would result in the pausing or stalling of translation apparatus at elongation and termination steps often occur1-6. Except for programmed stalling, which is usually utilized by the cells to exert regulatory purposes5,7,8, ribosomes stalled on mRNAs need to be terminated and recycled to maintain adequate cellular translation capacity9. A large source of ribosome stalling originates in aberrant mRNAs that lack a stop codon. Transcriptional errors and misprocessing of primary transcripts, as well as undesired mRNA cleavage, all contribute to the formation of non-stop mRNAs. Ribosomes stalled on the 3'-end of non-stop mRNAs do not undergo normal termination due to the lack of specific stop-codon recognition by canonical peptide release factors at the A-site decoding center. In all bacteria, a well-characterized rescue system, tmRNA/SmpB-mediated trans-translation, functions to reroute stalled ribosomes to the normal elongation cycle and termination3,4,10-12. Two additional rescue systems, ArfA/RF213-16 and ArfB (YaeJ)17,18 that work independently of tmRNA, are present in some bacterial species, but their mechanisms are not fully understood. Here, we characterize, by cryo-electron microscopy, a structure of the E. coli 70S ribosome bound with ArfA, RF2, a short non-stop mRNA and a cognate P-site tRNA. Our structure reveals that the C-terminal loop of ArfA occupies the mRNA entry channel on the 30S subunit, while its N-terminus is sandwiched between the decoding center and the switch loop of RF2, leading to dramatic conformational changes of both. Despite the distinct conformation of RF2, the conserved GGQ motif of RF2 is precisely positioned next to the CCA-end of P-site tRNA. These data illustrate a stop-codon surrogate mechanism for ArfA in facilitating the termination of non-stop ribosomal complex by RF2. Mechanistic insights into the alternative translation termination by ArfA and RF2.,Ma C, Kurita D, Li N, Chen Y, Himeno H, Gao N Nature. 2016 Dec 1. doi: 10.1038/nature20822. PMID:27906160[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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