Open Access

Nature Communications, volume 7, issue 1, publication number 12026

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

Arenz Stefan ¹

Bock Lars V ²

Gräf Michael ¹

Innis C Axel ^{3, 4, 5}

Beckmann Roland ^{1, 6}

Grubmüller Helmut ²

Vaiana Andrea C ²

Wilson Daniel N. ^{1, 6}

Hide authors affiliations Show authors affiliations: 6 affiliations

Gene Center and Department for Biochemistry, University of Munich, Munich, Germany |

Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany |

Institut Européen de Chimie et Biologie, University of Bordeaux, Pessac, France |

⁴

INSERM U1212, Bordeaux, France |

⁵

CNRS UMR7377, Bordeaux, France |

⁶

Center for integrated Protein Science Munich, University of Munich, Munich, Germany |

Publication type: Journal Article

Publication date: 2016-07-06

Springer Nature

Journal: Nature Communications

Quartile SCImago

Quartile WOS

Impact factor: 16.6

ISSN: 20411723

DOI: 10.1038/ncomms12026

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PubMed ID: 27380950

General Chemistry

General Biochemistry, Genetics and Molecular Biology

General Physics and Astronomy

Abstract

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

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Springer Nature	Springer Nature, 22, 21.78% Springer Nature 22 publications, 21.78%
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American Chemical Society (ACS)	American Chemical Society (ACS), 7, 6.93% American Chemical Society (ACS) 7 publications, 6.93%
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Public Library of Science (PLoS)	Public Library of Science (PLoS), 2, 1.98% Public Library of Science (PLoS) 2 publications, 1.98%
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eLife Sciences Publications	eLife Sciences Publications, 2, 1.98% eLife Sciences Publications 2 publications, 1.98%
International Union of Crystallography (IUCr)	International Union of Crystallography (IUCr), 1, 0.99% International Union of Crystallography (IUCr) 1 publication, 0.99%
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Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 1, 0.99% Multidisciplinary Digital Publishing Institute (MDPI) 1 publication, 0.99%
American Society of Plant Biologists	American Society of Plant Biologists, 1, 0.99% American Society of Plant Biologists 1 publication, 0.99%
Pleiades Publishing	Pleiades Publishing, 1, 0.99% Pleiades Publishing 1 publication, 0.99%
Wiley	Wiley, 1, 0.99% Wiley 1 publication, 0.99%
Rockefeller University Press	Rockefeller University Press, 1, 0.99% Rockefeller University Press 1 publication, 0.99%
	5 10 15 20 25

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Arenz S. et al. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest // Nature Communications. 2016. Vol. 7. No. 1. 12026

GOST all authors (up to 50) Copy

Arenz S., Bock L. V., Gräf M., Innis C. A., Beckmann R., Grubmüller H., Vaiana A. C., Wilson D. N. A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest // Nature Communications. 2016. Vol. 7. No. 1. 12026

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/ncomms12026

UR - https://doi.org/10.1038%2Fncomms12026

TI - A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

T2 - Nature Communications

AU - Arenz, Stefan

AU - Bock, Lars V

AU - Gräf, Michael

AU - Innis, C Axel

AU - Beckmann, Roland

AU - Grubmüller, Helmut

AU - Vaiana, Andrea C

AU - Wilson, Daniel N.

PY - 2016

DA - 2016/07/06 00:00:00

PB - Springer Nature

IS - 1

VL - 7

PMID - 27380950

SN - 2041-1723

ER -

BibTex

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BibTex Copy

@article{2016_Arenz,

author = {Stefan Arenz and Lars V Bock and Michael Gräf and C Axel Innis and Roland Beckmann and Helmut Grubmüller and Andrea C Vaiana and Daniel N. Wilson},

title = {A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest},

journal = {Nature Communications},

year = {2016},

volume = {7},

publisher = {Springer Nature},

month = {jul},

url = {https://doi.org/10.1038%2Fncomms12026},

number = {1},

doi = {10.1038/ncomms12026}

}

Found error?

Publisher

Springer Nature

Journal

Nature Communications

Quartile SCImago

Quartile WOS

Impact factor

16.6

ISSN

20411723 (Print)