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Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes

Overview
Journal Cell
Publisher Cell Press
Specialty Cell Biology
Date 2016 Nov 19
PMID 27863242
Citations 120
Authors
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Abstract

In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code on ribosomes. We present structures of the mammalian ribosome engaged with decoding factor⋅GTPase complexes representing intermediates of translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and ribosome rescue (Pelota⋅Hbs1l). Comparative analyses reveal that each decoding factor exploits the plasticity of the ribosomal decoding center to differentially remodel ribosomal proteins and rRNA. This leads to varying degrees of large-scale ribosome movements and implies distinct mechanisms for communicating information from the decoding center to each GTPase. Additional structural snapshots of the translation termination pathway reveal the conformational changes that choreograph the accommodation of decoding factors into the peptidyl transferase center. Our results provide a structural framework for how different states of the mammalian ribosome are selectively recognized by the appropriate decoding factor⋅GTPase complex to ensure translational fidelity.

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References
1.
Amunts A, Brown A, Bai X, Llacer J, Hussain T, Emsley P . Structure of the yeast mitochondrial large ribosomal subunit. Science. 2014; 343(6178):1485-1489. PMC: 4046073. DOI: 10.1126/science.1249410. View

2.
Voorhees R, Schmeing T, Kelley A, Ramakrishnan V . The mechanism for activation of GTP hydrolysis on the ribosome. Science. 2010; 330(6005):835-838. PMC: 3763471. DOI: 10.1126/science.1194460. View

3.
Alksne L, Anthony R, Liebman S, Warner J . An accuracy center in the ribosome conserved over 2 billion years. Proc Natl Acad Sci U S A. 1993; 90(20):9538-41. PMC: 47604. DOI: 10.1073/pnas.90.20.9538. View

4.
Emsley P, Lohkamp B, Scott W, Cowtan K . Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. PMC: 2852313. DOI: 10.1107/S0907444910007493. View

5.
Loenarz C, Sekirnik R, Thalhammer A, Ge W, Spivakovsky E, Mackeen M . Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy. Proc Natl Acad Sci U S A. 2014; 111(11):4019-24. PMC: 3964080. DOI: 10.1073/pnas.1311750111. View