Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation Elongation Factor EF-P.

Molecular cell 2017 Nov 02

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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. Copyright © 2017 Elsevier Inc. All rights reserved.

Citation

Paul Huter, Stefan Arenz, Lars V Bock, Michael Graf, Jan Ole Frister, Andre Heuer, Lauri Peil, Agata L Starosta, Ingo Wohlgemuth, Frank Peske, Jiří Nováček, Otto Berninghausen, Helmut Grubmüller, Tanel Tenson, Roland Beckmann, Marina V Rodnina, Andrea C Vaiana, Daniel N Wilson. Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation Elongation Factor EF-P. Molecular cell. 2017 Nov 02;68(3):515-527.e6