7ac7

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Structure of accomodated trans-translation complex on E. Coli stalled ribosome.

Structural highlights

7ac7 is a 10 chain structure with sequence from Escherichia coli and Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.08Å
Ligands:0TD, 1MG, 2MA, 2MG, 3AU, 3TD, 4D4, 4OC, 4SU, 5MC, 5MU, 6MZ, G7M, H2U, MA6, MG, MIA, OMC, OMG, OMU, PSU, UR3, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SSRP_ECOLI Required for rescue of stalled ribosomes mediated by trans-translation. Binds to tmRNA RNA (also known as SsrA or 10Sa RNA, 363 nucleotides in this organism), required for stable binding of tmRNA to ribosomes (PubMed:10393194, PubMed:11904185, PubMed:11917023). tmRNA and SmpB together mimic tRNA shape, replacing the anticodon stem-loop with SmpB (Probable). tmRNA is encoded by the ssrA gene; the 2 termini fold to resemble tRNA(Ala) and it encodes a 'tag peptide', a short internal open reading frame. Able to recruit charged tmRNA to ribosomes (PubMed:15069072). Does not play a role in transcription, processing or Ala-aminoacylation of tmRNA (PubMed:10393194). Other studies have shown it stimulates aminoacylation of tmRNA (PubMed:11917023, PubMed:11904185). May protect tmRNA from degradation (PubMed:11917023). Binds to tmRNA that cannot be aminoacylated (tmRNA G3A), does not bind to tmRNA mutations near the tRNA-like termini (tmRNA G19C, A334U); other tmRNA mutations that block trans-translation still bind SmpB (PubMed:11917023). With tmRNA may play a role in bacterial persistence (PubMed:23812681). During trans-translation Ala-aminoacylated transfer-messenger RNA acts like a tRNA, entering the A-site of stalled ribosomes, displacing the stalled mRNA. The ribosome then switches to translate the ORF on the tmRNA, the nascent peptide is terminated with the 'tag peptide' encoded by the tmRNA and targeted for degradation. The ribosome is freed to recommence translation, which seems to be the essential function of trans-translation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]

Publication Abstract from PubMed

In bacteria, trans-translation is the main rescue system, freeing ribosomes stalled on defective messenger RNAs. This mechanism is driven by small protein B (SmpB) and transfer-messenger RNA (tmRNA), a hybrid RNA known to have both a tRNA-like and an mRNA-like domain. Here we present four cryo-EM structures of the ribosome during trans-translation at resolutions from 3.0 to 3.4 A. These include the high-resolution structure of the whole pre-accommodated state, as well as structures of the accommodated state, the translocated state, and a translocation intermediate. Together, they shed light on the movements of the tmRNA-SmpB complex in the ribosome, from its delivery by the elongation factor EF-Tu to its passage through the ribosomal A and P sites after the opening of the B1 bridges. Additionally, we describe the interactions between the tmRNA-SmpB complex and the ribosome. These explain why the process does not interfere with canonical translation.

Structures of tmRNA and SmpB as they transit through the ribosome.,Guyomar C, D'Urso G, Chat S, Giudice E, Gillet R Nat Commun. 2021 Aug 13;12(1):4909. doi: 10.1038/s41467-021-24881-4. PMID:34389707[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
3 reviews cite this structure
<i>Trans</i>-Translation Is an Appealing Target for the Development of New Antimicrobial Compounds.
Campos-Silva et al. (2021)
2 more
12 other articles
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See Also

References

  1. ↑ Karzai AW, Susskind MM, Sauer RT. SmpB, a unique RNA-binding protein essential for the peptide-tagging activity of SsrA (tmRNA). EMBO J. 1999 Jul 1;18(13):3793-9. PMID:10393194 doi:http://dx.doi.org/10.1093/emboj/18.13.3793
  2. ↑ Shimizu Y, Ueda T. The role of SmpB protein in trans-translation. FEBS Lett. 2002 Mar 6;514(1):74-7. PMID:11904185
  3. ↑ Hanawa-Suetsugu K, Takagi M, Inokuchi H, Himeno H, Muto A. SmpB functions in various steps of trans-translation. Nucleic Acids Res. 2002 Apr 1;30(7):1620-9. PMID:11917023
  4. ↑ Hallier M, Ivanova N, Rametti A, Pavlov M, Ehrenberg M, Felden B. Pre-binding of small protein B to a stalled ribosome triggers trans-translation. J Biol Chem. 2004 Jun 18;279(25):25978-85. doi: 10.1074/jbc.M314086200. Epub 2004, Apr 6. PMID:15069072 doi:http://dx.doi.org/10.1074/jbc.M314086200
  5. ↑ Sundermeier TR, Dulebohn DP, Cho HJ, Karzai AW. A previously uncharacterized role for small protein B (SmpB) in transfer messenger RNA-mediated trans-translation. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2316-21. doi:, 10.1073/pnas.0409694102. Epub 2005 Feb 7. PMID:15699355 doi:http://dx.doi.org/10.1073/pnas.0409694102
  6. ↑ Kurita D, Muto A, Himeno H. Role of the C-terminal tail of SmpB in the early stage of trans-translation. RNA. 2010 May;16(5):980-90. doi: 10.1261/rna.1916610. Epub 2010 Mar 26. PMID:20348441 doi:http://dx.doi.org/10.1261/rna.1916610
  7. ↑ Fu J, Hashem Y, Wower I, Lei J, Liao HY, Zwieb C, Wower J, Frank J. Visualizing the transfer-messenger RNA as the ribosome resumes translation. EMBO J. 2010 Nov 17;29(22):3819-25. Epub 2010 Oct 12. PMID:20940705 doi:10.1038/emboj.2010.255
  8. ↑ Ramrath DJ, Yamamoto H, Rother K, Wittek D, Pech M, Mielke T, Loerke J, Scheerer P, Ivanov P, Teraoka Y, Shpanchenko O, Nierhaus KH, Spahn CM. The complex of tmRNA-SmpB and EF-G on translocating ribosomes. Nature. 2012 May 6;485(7399):526-9. doi: 10.1038/nature11006. PMID:22622583 doi:10.1038/nature11006
  9. ↑ Li J, Ji L, Shi W, Xie J, Zhang Y. Trans-translation mediates tolerance to multiple antibiotics and stresses in Escherichia coli. J Antimicrob Chemother. 2013 Nov;68(11):2477-81. doi: 10.1093/jac/dkt231. Epub, 2013 Jun 27. PMID:23812681 doi:http://dx.doi.org/10.1093/jac/dkt231
  10. ↑ Fu J, Hashem Y, Wower I, Lei J, Liao HY, Zwieb C, Wower J, Frank J. Visualizing the transfer-messenger RNA as the ribosome resumes translation. EMBO J. 2010 Nov 17;29(22):3819-25. Epub 2010 Oct 12. PMID:20940705 doi:10.1038/emboj.2010.255
  11. ↑ Guyomar C, D'Urso G, Chat S, Giudice E, Gillet R. Structures of tmRNA and SmpB as they transit through the ribosome. Nat Commun. 2021 Aug 13;12(1):4909. PMID:34389707 doi:10.1038/s41467-021-24881-4

Contents


PDB ID 7ac7

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