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Profiling Ssb-nascent chain interactions reveals principles of Hsp70-assisted folding

The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic,...

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Hauptverfasser: Döring, Kristina (VerfasserIn) , Vainshtein, Yevhen (VerfasserIn) , Mayer, Matthias P. (VerfasserIn) , Kramer, Günter (VerfasserIn) , Bukau, Bernd (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2017
In: Cell
Year: 2017, Jahrgang: 170, Heft: 2, Pages: 298-311
ISSN:1097-4172
DOI:10.1016/j.cell.2017.06.038
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1016/j.cell.2017.06.038
Verlag, Volltext: http://linkinghub.elsevier.com/retrieve/pii/S0092867417307572
Volltext
Verfasserangaben:Kristina Döring, Nabeel Ahmed, Trine Riemer, Harsha Garadi Suresh, Yevhen Vainshtein, Markus Habich, Jan Riemer, Matthias P. Mayer, Edward P. O’Brien, Günter Kramer, Bernd Bukau
Beschreibung
Zusammenfassung:The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic, nuclear, and hitherto unknown substrate classes of mitochondrial and endoplasmic reticulum (ER) nascent proteins, supporting its general chaperone function. Ssb engages most substrates by multiple binding-release cycles to a degenerate sequence enriched in positively charged and aromatic amino acids. Timely association with this motif upon emergence at the ribosomal tunnel exit requires ribosome-associated complex (RAC) but not nascent polypeptide-associated complex (NAC). Ribosome footprint densities along orfs reveal faster translation at times of Ssb binding, mainly imposed by biases in mRNA secondary structure, codon usage, and Ssb action. Ssb thus employs substrate-tailored dynamic nascent chain associations to coordinate co-translational protein folding, facilitate accelerated translation, and support membrane targeting of organellar proteins.
Beschreibung:Available online 14 July 2017
Gesehen am 27.06.2018
Beschreibung:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2017.06.038

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