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Lookup NU author(s): Dr Agata Starosta
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© 2017 Elsevier Inc. Ribosomes synthesizing proteins containing consecutive proline residues become stalled and require rescue via the action of uniquely modified translation elongation factors, EF-P in bacteria, or archaeal/eukaryotic a/eIF5A. To date, no structures exist of EF-P or eIF5A in complex with translating ribosomes stalled at polyproline stretches, and thus structural insight into how EF-P/eIF5A rescue these arrested ribosomes has been lacking. Here we present cryo-EM structures of ribosomes stalled on proline stretches, without and with modified EF-P. The structures suggest that the favored conformation of the polyproline-containing nascent chain is incompatible with the peptide exit tunnel of the ribosome and leads to destabilization of the peptidyl-tRNA. Binding of EF-P stabilizes the P-site tRNA, particularly via interactions between its modification and the CCA end, thereby enforcing an alternative conformation of the polyproline-containing nascent chain, which allows a favorable substrate geometry for peptide bond formation. Huter et al. present cryo-EM structures of polyproline-stalled ribosomes in the presence and absence of translation elongation factor EF-P. The structures reveal that polyproline sequences arrest translation by destabilizing the P-site tRNA, whereas binding of EF-P stabilizes the P-site tRNA and promotes a favorable geometry for peptide bond formation.
Author(s): Huter P, Arenz S, Bock LV, Graf M, Frister JO, Heuer A, Peil L, Starosta AL, Wohlgemuth I, Peske F, Novacek J, Berninghausen O, Grubmuller H, Tenson T, Beckmann R, Rodnina MV, Vaiana AC, Wilson DN
Publication type: Article
Publication status: Published
Journal: Molecular Cell
Year: 2017
Volume: 68
Issue: 3
Pages: 515-527.e6
Print publication date: 02/11/2017
Online publication date: 02/11/2017
Acceptance date: 11/10/2017
ISSN (print): 1097-2765
ISSN (electronic): 1097-4164
Publisher: Cell Press
URL: https://doi.org/10.1016/j.molcel.2017.10.014
DOI: 10.1016/j.molcel.2017.10.014
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