Dynamics of uS19 C-Terminal Tail during the Translation Elongation Cycle in Human Ribosomes.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
07 04 2020
Historique:
received: 21 06 2019
revised: 06 12 2019
accepted: 12 03 2020
entrez: 9 4 2020
pubmed: 9 4 2020
medline: 28 4 2021
Statut: ppublish

Résumé

Ribosomes undergo multiple conformational transitions during translation elongation. Here, we report the high-resolution cryoelectron microscopy (cryo-EM) structure of the human 80S ribosome in the post-decoding pre-translocation state (classical-PRE) at 3.3-Å resolution along with the rotated (hybrid-PRE) and the post-translocation states (POST). The classical-PRE state ribosome structure reveals a previously unobserved interaction between the C-terminal region of the conserved ribosomal protein uS19 and the A- and P-site tRNAs and the mRNA in the decoding site. In addition to changes in the inter-subunit bridges, analysis of different ribosomal conformations reveals the dynamic nature of this domain and suggests a role in tRNA accommodation and translocation during elongation. Furthermore, we show that disease-associated mutations in uS19 result in increased frameshifting. Together, this structure-function analysis provides mechanistic insights into the role of the uS19 C-terminal tail in the context of mammalian ribosomes.

Identifiants

pubmed: 32268098
pii: S2211-1247(20)30351-X
doi: 10.1016/j.celrep.2020.03.037
pii:
doi:

Substances chimiques

RNA, Messenger 0
Ribosomal Proteins 0
ribosomal protein S19 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107473

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Varun Bhaskar (V)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Alexandra Graff-Meyer (A)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Andreas D Schenk (AD)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Simone Cavadini (S)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Ottilie von Loeffelholz (O)

Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France; Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, Illkirch, France; Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France; Université de Strasbourg, Illkirch, France.

S Kundhavai Natchiar (SK)

Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France; Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, Illkirch, France; Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France; Université de Strasbourg, Illkirch, France.

Caroline G Artus-Revel (CG)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Hans-Rudolf Hotz (HR)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.

Gabriel Bretones (G)

Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.

Bruno P Klaholz (BP)

Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, INSERM, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France; Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, Illkirch, France; Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France; Université de Strasbourg, Illkirch, France.

Jeffrey A Chao (JA)

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Electronic address: jeffrey.chao@fmi.ch.

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Classifications MeSH