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

CSLog in Log in (EduId)

Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation ...

Přehled o publikaci

J 2017

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

HUTER, P.; S. ARENZ; L.V. BOCK; M. GRAF; J.O. FRISTER et. al.

Basic information

Original name

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

Authors

Edition

Molecular Cell, CAMBRIDGE, CELL PRESS, 2017, 1097-2765

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

RIV identification code

RIV/00216224:14740/17:00100397

Organization

Středoevropský technologický institut – Repository – Repository

UT WoS

000414250700007

Keywords in English

PEPTIDE-BOND FORMATION; AMINOACYL-TRANSFER-RNA; MOLECULAR-DYNAMICS; PROTEIN-SYNTHESIS; 70S RIBOSOME; CRYO-EM; CRYSTAL-STRUCTURE; PROLINE RESIDUES; FACTOR EIF5A; MECHANISM

Links

LM2015043, research and development project.

Changed: 5/9/2020 12:41, RNDr. Daniel Jakubík

Abstract

In the original language

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.

Files attached

https://is.muni.cz/publication/1411418/Huter_EFP_text_figures_110817_LR.pdf File version

Cite

HUTER, P.; S. ARENZ; L.V. BOCK; M. GRAF; J.O. FRISTER; A. HEUER; L. PEIL; A.L. STAROSTA; I. WOHLGEMUTH; F. PESKE; Jiří NOVÁČEK; O. BERNINGHAUSEN; H. GRUBMULLER; T. TENSON; R. BECKMANN; M.V. RODNINA; A.C. VAIANA and D.N. WILSON. Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation Elongation Factor EF-P. Molecular Cell. CAMBRIDGE: CELL PRESS, 2017, vol. 68, No 3, p. 515-533. ISSN 1097-2765.

@article{39963,
   author = {Huter, P. and Arenz, S. and Bock, L.V. and Graf, M. and Frister, J.O. and Heuer, A. and Peil, L. and Starosta, A.L. and Wohlgemuth, I. and Peske, F. and Nováček, Jiří and Berninghausen, O. and Grubmuller, H. and Tenson, T. and Beckmann, R. and Rodnina, M.V. and Vaiana, A.C. and Wilson, D.N.},
   article_location = {CAMBRIDGE},
   article_number = {3},
   keywords = {PEPTIDE-BOND FORMATION; AMINOACYL-TRANSFER-RNA; MOLECULAR-DYNAMICS; PROTEIN-SYNTHESIS; 70S RIBOSOME; CRYO-EM; CRYSTAL-STRUCTURE; PROLINE RESIDUES; FACTOR EIF5A; MECHANISM},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation Elongation Factor EF-P},
   url = {https://www.sciencedirect.com/science/article/pii/S109727651730789X?via%3Dihub},
   volume = {68},
   year = {2017}
}

TY  - JOUR
ID  - 39963
AU  - 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.
PY  - 2017
TI  - Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation Elongation Factor EF-P
JF  - Molecular Cell
VL  - 68
IS  - 3
SP  - 515
EP  - 515
PB  - CELL PRESS
SN  - 1097-2765
KW  - PEPTIDE-BOND FORMATION
KW  - AMINOACYL-TRANSFER-RNA
KW  - MOLECULAR-DYNAMICS
KW  - PROTEIN-SYNTHESIS
KW  - 70S RIBOSOME
KW  - CRYO-EM
KW  - CRYSTAL-STRUCTURE
KW  - PROLINE RESIDUES
KW  - FACTOR EIF5A
KW  - MECHANISM
UR  - https://www.sciencedirect.com/science/article/pii/S109727651730789X?via%3Dihub
N2  - 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.
ER  -

HUTER, P.; S. ARENZ; L.V. BOCK; M. GRAF; J.O. FRISTER; A. HEUER; L. PEIL; A.L. STAROSTA; I. WOHLGEMUTH; F. PESKE; Jiří NOVÁČEK; O. BERNINGHAUSEN; H. GRUBMULLER; T. TENSON; R. BECKMANN; M.V. RODNINA; A.C. VAIANA and D.N. WILSON. Structural Basis for Polyproline-Mediated Ribosome Stalling and Rescue by the Translation Elongation Factor EF-P. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2017, vol.~68, No~3, p.~515-533. ISSN~1097-2765.