Early Scanning of Nascent Polypeptides inside the Ribosomal Tunnel by NAC

Molecular Cell
Martin GamerdingerElke Deuerling

Abstract

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.

References

May 1, 1974·Genetics·S Brenner
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·B LauringM Wiedmann
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·R GeorgeT Lithgow
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·I MöllerB Lauring
Dec 22, 1999·Journal of Structural Biology·S J LudtkeW Chiu
Jun 8, 2001·Annual Review of Biochemistry·R J KeenanP Walter
Jun 5, 2003·Journal of Structural Biology·Joseph A Mindell, Nikolaus Grigorieff
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Dec 1, 2005·The Journal of Biological Chemistry·Renee D WegrzynElke Deuerling
Mar 24, 2006·Nature Methods·Youngha Ryu, Peter G Schultz
Oct 3, 2006·Journal of Structural Biology·J Bernard Heymann, David M Belnap
Apr 5, 2007·Nature Protocols·Andrej ShevchenkoMatthias Mann
May 24, 2008·The EMBO Journal·Frieder MerzElke Deuerling
Apr 27, 2010·Methods in Molecular Biology·Ajay SharmaRamanujan S Hegde
Feb 1, 2011·Nature Methods·Stefanie RedemannHenrik Bringmann
Nov 1, 2011·Journal of the American Society for Mass Spectrometry·Michael GötzeAndrea Sinz
Apr 17, 2012·Trends in Biochemical Sciences·Steffen Preissler, Elke Deuerling
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
Oct 3, 2012·Cold Spring Harbor Perspectives in Biology·Diana StojanovskiMartin van der Laan
Nov 13, 2012·Nature Structural & Molecular Biology·Basil J GreberNenad Ban
Feb 12, 2013·Molecular Cell·Sebastian PechmannJudith Frydman
Apr 16, 2013·Molecular Cell·Stefanie DuttlerJudith Frydman
Apr 16, 2013·Molecular Cell·Feng WangJon M Huibregtse
Apr 23, 2013·The EMBO Journal·Janine Kirstein-MilesRichard I Morimoto
Aug 21, 2013·Journal of Structural Biology·Giovanni CardoneAlasdair C Steven
Nov 12, 2013·Nature Methods·Alp KucukelbirHemant D Tagare
May 14, 2014·Nature Methods·Christian Frøkjær-JensenErik M Jorgensen
Jun 17, 2014·Cell·Rebecca M VoorheesRamanujan S Hegde
Nov 5, 2014·Nature Structural & Molecular Biology·Yixiao ZhangNing Gao

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Citations

Nov 16, 2019·Science·Zhewang LinRamanujan S Hegde
Mar 7, 2020·Biological Chemistry·Maria Clara Avendaño-MonsalveSoledad Funes
Aug 8, 2020·Genetics·Thorsten Hoppe, Ehud Cohen
Aug 4, 2020·ELife·Niladri K SinhaRachel Green
Feb 6, 2021·Nature Communications·Ying ZhangSabine Rospert
Dec 8, 2020·Biochemistry. Biokhimii︠a︡·Z Z KhairullinaN V Sumbatyan
May 15, 2020·Current Opinion in Cell Biology·Ben P PhillipsElizabeth A Miller
May 8, 2021·The FEBS Journal·Sarah O'KeefeStephen High
Sep 25, 2021·Nature Reviews. Molecular Cell Biology·Ramanujan S Hegde, Robert J Keenan

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