Doering, Kristina, Ahmed, Nabeel, Riemer, Trine, Suresh, Harsha Garadi, Vainshtein, Yevhen ORCID: 0000-0001-7944-8892, Habich, Markus, Riemer, Jan, Mayer, Matthias P., O'Brien, Edward P., Kramer, Guenter and Bukau, Bernd ORCID: 0000-0003-0521-7199 (2017). Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding. Cell, 170 (2). S. 298 - 332. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Doering, KristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahmed, NabeelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemer, TrineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suresh, Harsha GaradiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vainshtein, YevhenUNSPECIFIEDorcid.org/0000-0001-7944-8892UNSPECIFIED
Habich, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemer, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayer, Matthias P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Brien, Edward P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramer, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bukau, BerndUNSPECIFIEDorcid.org/0000-0003-0521-7199UNSPECIFIED
URN: urn:nbn:de:hbz:38-225001
DOI: 10.1016/j.cell.2017.06.038
Journal or Publication Title: Cell
Volume: 170
Number: 2
Page Range: S. 298 - 332
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RIBOSOME-ASSOCIATED COMPLEX; MOLECULAR CHAPERONE SSB; HSP70 HOMOLOG SSB; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; TRIGGER FACTOR; HEAT-SHOCK; COTRANSLATIONAL CHAPERONE; TRANSLATION TERMINATION; EUKARYOTIC RIBOSOMEMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22500

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