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

• Autoři: HUTER P.; ARENZ S.; BOCK L.V.; GRAF M.; FRISTER J.O.; HEUER A.; PEIL L.; STAROSTA A.L.; WOHLGEMUTH I.; PESKE F.; NOVÁČEK Jiří; BERNINGHAUSEN O.; GRUBMULLER H.; TENSON T.; BECKMANN R.; RODNINA M.V.; VAIANA A.C.; WILSON D.N.
• Rok publikování: 2017
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Molecular Cell
• Fakulta / Pracoviště MU: Středoevropský technologický institut
• www: https://www.sciencedirect.com/science/article/pii/S109727651730789X?via%3Dihub
• Doi: http://dx.doi.org/10.1016/j.molcel.2017.10.014
• Klíčová slova: PEPTIDE-BOND FORMATION; AMINOACYL-TRANSFER-RNA; MOLECULAR-DYNAMICS; PROTEIN-SYNTHESIS; 70S RIBOSOME; CRYO-EM; CRYSTAL-STRUCTURE; PROLINE RESIDUES; FACTOR EIF5A; MECHANISM

Přiložené soubory

• Huter_EFP_text_figures_110817_LR.pdf

• Popis: 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 peptidyltRNA. 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.

Související projekty

• Czech Infrastructure for Integrative Structural Biology