Structure of the Mammalian Ribosomal Pre-termination Complex Associated with ERF1.eRF3.GDPNP

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Dec 17

PMID 24335085

Citations 46

Authors

Amedee des Georges

Yaser Hashem

Anett Unbehaun

Robert A Grassucci

Derek Taylor

Christopher U T Hellen

Tatyana V Pestova

Joachim Frank

Affiliations

Soon will be listed here.

Abstract

Eukaryotic translation termination results from the complex functional interplay between two release factors, eRF1 and eRF3, in which GTP hydrolysis by eRF3 couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, we present a cryo-electron microscopy structure of pre-termination complexes associated with eRF1•eRF3•GDPNP at 9.7 -Å resolution, which corresponds to the initial pre-GTP hydrolysis stage of factor attachment and stop codon recognition. It reveals the ribosomal positions of eRFs and provides insights into the mechanisms of stop codon recognition and triggering of eRF3's GTPase activity.

Citing Articles

Ribosomal A-site interactions with near-cognate tRNAs drive stop codon readthrough.

capkova Pavlikova Z, Miletinova P, Roithova A, Pospisilova K, Zahonova K, Kachale A Nat Struct Mol Biol. 2025; .

PMID: 39806023 DOI: 10.1038/s41594-024-01450-z.

The ABCF ATPase New1 resolves translation termination defects associated with specific tRNAArg and tRNALys isoacceptors in the P site.

Turnbull K, Paternoga H, von der Weth E, Egorov A, Pochopien A, Zhang Y Nucleic Acids Res. 2024; 52(19):12005-12020.

PMID: 39217469 PMC: 11514491. DOI: 10.1093/nar/gkae748.

Functional Activity of Isoform 2 of Human eRF1.

Shuvalov A, Klishin A, Biziaev N, Shuvalova E, Alkalaeva E Int J Mol Sci. 2024; 25(14).

PMID: 39063238 PMC: 11277123. DOI: 10.3390/ijms25147997.

The ABCF ATPase New1 resolves translation termination defects associated with specific tRNA and tRNA isoacceptors in the P site.

Turnbull K, Paternoga H, von der Weth E, Egorov A, Pochopien A, Zhang Y bioRxiv. 2024; .

PMID: 38854126 PMC: 11160720. DOI: 10.1101/2024.05.29.596377.

Cryo-EM reconstruction of the human 40S ribosomal subunit at 2.15 Å resolution.

Pellegrino S, Dent K, Spikes T, Warren A Nucleic Acids Res. 2023; 51(8):4043-4054.

PMID: 36951107 PMC: 10164566. DOI: 10.1093/nar/gkad194.

References

Fukunaga R, Yokoyama S . Aminoacylation complex structures of leucyl-tRNA synthetase and tRNALeu reveal two modes of discriminator-base recognition. Nat Struct Mol Biol. 2005; 12(10):915-22. DOI: 10.1038/nsmb985. View

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View

Taylor D, Unbehaun A, Li W, Das S, Lei J, Liao H . Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex. Proc Natl Acad Sci U S A. 2012; 109(45):18413-8. PMC: 3494903. DOI: 10.1073/pnas.1216730109. View

Pisareva V, Skabkin M, Hellen C, Pestova T, Pisarev A . Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes. EMBO J. 2011; 30(9):1804-17. PMC: 3101999. DOI: 10.1038/emboj.2011.93. View

Salas-Marco J, Bedwell D . GTP hydrolysis by eRF3 facilitates stop codon decoding during eukaryotic translation termination. Mol Cell Biol. 2004; 24(17):7769-78. PMC: 506980. DOI: 10.1128/MCB.24.17.7769-7778.2004. View

Shoemaker C, Eyler D, Green R . Dom34:Hbs1 promotes subunit dissociation and peptidyl-tRNA drop-off to initiate no-go decay. Science. 2010; 330(6002):369-72. PMC: 4022135. DOI: 10.1126/science.1192430. View

Frolova L, Tsivkovskii R, Sivolobova G, Oparina N, Serpinsky O, Blinov V . Mutations in the highly conserved GGQ motif of class 1 polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis. RNA. 1999; 5(8):1014-20. PMC: 1369825. DOI: 10.1017/s135583829999043x. View

Pintilie G, Zhang J, Goddard T, Chiu W, Gossard D . Quantitative analysis of cryo-EM density map segmentation by watershed and scale-space filtering, and fitting of structures by alignment to regions. J Struct Biol. 2010; 170(3):427-38. PMC: 2874196. DOI: 10.1016/j.jsb.2010.03.007. View

Laurberg M, Asahara H, Korostelev A, Zhu J, Trakhanov S, Noller H . Structural basis for translation termination on the 70S ribosome. Nature. 2008; 454(7206):852-7. DOI: 10.1038/nature07115. View

10.

Fischer N, Konevega A, Wintermeyer W, Rodnina M, Stark H . Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy. Nature. 2010; 466(7304):329-33. DOI: 10.1038/nature09206. View

11.

Bertram G, Bell H, Ritchie D, Fullerton G, Stansfield I . Terminating eukaryote translation: domain 1 of release factor eRF1 functions in stop codon recognition. RNA. 2000; 6(9):1236-47. PMC: 1369997. DOI: 10.1017/s1355838200000777. View

12.

Mottagui-Tabar S, Tuite M, ISAKSSON L . The influence of 5' codon context on translation termination in Saccharomyces cerevisiae. Eur J Biochem. 1998; 257(1):249-54. DOI: 10.1046/j.1432-1327.1998.2570249.x. View

13.

Skabkin M, Skabkina O, Hellen C, Pestova T . Reinitiation and other unconventional posttermination events during eukaryotic translation. Mol Cell. 2013; 51(2):249-64. PMC: 4038429. DOI: 10.1016/j.molcel.2013.05.026. View

14.

Weixlbaumer A, Jin H, Neubauer C, Voorhees R, Petry S, Kelley A . Insights into translational termination from the structure of RF2 bound to the ribosome. Science. 2008; 322(5903):953-6. PMC: 2642913. DOI: 10.1126/science.1164840. View

15.

Spahn C, Beckmann R, Eswar N, Penczek P, Sali A, Blobel G . Structure of the 80S ribosome from Saccharomyces cerevisiae--tRNA-ribosome and subunit-subunit interactions. Cell. 2001; 107(3):373-86. DOI: 10.1016/s0092-8674(01)00539-6. View

16.

Cheng Z, Saito K, Pisarev A, Wada M, Pisareva V, Pestova T . Structural insights into eRF3 and stop codon recognition by eRF1. Genes Dev. 2009; 23(9):1106-18. PMC: 2682955. DOI: 10.1101/gad.1770109. View

17.

Alkalaeva E, Pisarev A, Frolova L, Kisselev L, Pestova T . In vitro reconstitution of eukaryotic translation reveals cooperativity between release factors eRF1 and eRF3. Cell. 2006; 125(6):1125-36. DOI: 10.1016/j.cell.2006.04.035. View

18.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View

19.

Kushnirov V, Ter-Avanesyan M, Telckov M, Surguchov A, Smirnov V, Inge-Vechtomov S . Nucleotide sequence of the SUP2 (SUP35) gene of Saccharomyces cerevisiae. Gene. 1988; 66(1):45-54. DOI: 10.1016/0378-1119(88)90223-5. View

20.

Scheres S . A Bayesian view on cryo-EM structure determination. J Mol Biol. 2011; 415(2):406-18. PMC: 3314964. DOI: 10.1016/j.jmb.2011.11.010. View