| RRC ID |
84952
|
| 著者 |
Ando Y, Kobo A, Niwa T, Yamakawa A, Konoma S, Kobayashi Y, Nureki O, Taguchi H, Itoh Y, Chadani Y.
|
| タイトル |
A mini-hairpin shaped nascent peptide blocks translation termination by a distinct mechanism.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Protein synthesis by ribosomes produces functional proteins but also serves diverse regulatory functions, which depend on the coding amino acid sequences. Certain nascent peptides interact with the ribosome exit tunnel to arrest translation and modulate themselves or the expression of downstream genes. However, a comprehensive understanding of the mechanisms of such ribosome stalling and its regulation remains elusive. In this study, we systematically screen for unidentified ribosome arrest peptides through phenotypic evaluation, proteomics, and mass spectrometry analyses, leading to the discovery of the arrest peptides PepNL and NanCL in E. coli. Our cryo-EM study on PepNL reveals a distinct arrest mechanism, in which the N-terminus of PepNL folds back towards the tunnel entrance to prevent the catalytic GGQ motif of the release factor from accessing the peptidyl transferase center, causing translation arrest at the UGA stop codon. Furthermore, unlike sensory arrest peptides that require an arrest inducer, PepNL uses tryptophan as an arrest inhibitor, where Trp-tRNATrp reads through the stop codon. Our findings illuminate the mechanism and regulatory framework of nascent peptide-induced translation arrest, paving the way for exploring regulatory nascent peptides.
|
| 巻・号 |
16(1)
|
| ページ |
2323
|
| 公開日 |
2025-3-8
|
| DOI |
10.1038/s41467-025-57659-z
|
| PII |
10.1038/s41467-025-57659-z
|
| PMID |
40057501
|
| PMC |
PMC11890864
|
| MeSH |
Codon, Terminator / genetics
Codon, Terminator / metabolism
Cryoelectron Microscopy
Escherichia coli* / genetics
Escherichia coli* / metabolism
Escherichia coli Proteins* / chemistry
Escherichia coli Proteins* / genetics
Escherichia coli Proteins* / metabolism
Peptide Chain Termination, Translational*
Peptide Termination Factors / metabolism
Peptides* / chemistry
Peptides* / metabolism
Protein Biosynthesis
Proteomics
Ribosomes / genetics
Ribosomes / metabolism
|
| IF |
12.121
|
| リソース情報 |
| 原核生物(大腸菌) |
ME9062 |
