Early Scanning of Nascent Polypeptides inside the Ribosomal Tunnel by NAC.


Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
05 09 2019
Historique:
received: 01 02 2019
revised: 08 05 2019
accepted: 19 06 2019
pubmed: 5 8 2019
medline: 30 1 2020
entrez: 5 8 2019
Statut: ppublish

Résumé

Cotranslational processing of newly synthesized proteins is fundamental for correct protein maturation. Protein biogenesis factors are thought to bind nascent polypeptides not before they exit the ribosomal tunnel. Here, we identify a nascent chain recognition mechanism deep inside the ribosomal tunnel by an essential eukaryotic cytosolic chaperone. The nascent polypeptide-associated complex (NAC) inserts the N-terminal tail of its β subunit (N-βNAC) into the ribosomal tunnel to sense substrates directly upon synthesis close to the peptidyl-transferase center. N-βNAC escorts the growing polypeptide to the cytosol and relocates to an alternate binding site on the ribosomal surface. Using C. elegans as an in vivo model, we demonstrate that the tunnel-probing activity of NAC is essential for organismal viability and critical to regulate endoplasmic reticulum (ER) protein transport by controlling ribosome-Sec61 translocon interactions. Thus, eukaryotic protein maturation relies on the early sampling of nascent chains inside the ribosomal tunnel.

Identifiants

pubmed: 31377116
pii: S1097-2765(19)30487-3
doi: 10.1016/j.molcel.2019.06.030
pii:
doi:

Substances chimiques

Caenorhabditis elegans Proteins 0
SEC Translocation Channels 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

996-1006.e8

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Martin Gamerdinger (M)

Department of Biology, Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany. Electronic address: martin.gamerdinger@uni-konstanz.de.

Kan Kobayashi (K)

Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland.

Annalena Wallisch (A)

Department of Biology, Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.

Stefan G Kreft (SG)

Department of Biology, Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.

Carolin Sailer (C)

Department of Biology, University of Konstanz, 78457 Konstanz, Germany.

Renate Schlömer (R)

Department of Biology, Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.

Nadine Sachs (N)

Department of Biology, Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany.

Ahmad Jomaa (A)

Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland.

Florian Stengel (F)

Department of Biology, University of Konstanz, 78457 Konstanz, Germany.

Nenad Ban (N)

Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: ban@mol.biol.ethz.ch.

Elke Deuerling (E)

Department of Biology, Molecular Microbiology, University of Konstanz, 78457 Konstanz, Germany. Electronic address: elke.deuerling@uni-konstanz.de.

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Classifications MeSH