Cotranslational Protein Folding inside the Ribosome Exit Tunnel

Ola B. Nilsson, Rickard Hedman, Jacopo Marino, Stephan Wickles, Lukas Bischoff, Magnus Johansson, Annika Müller-Lucks, Fabio Trovato, Joseph D. Puglisi, Edward P. O'Brien, Roland Beckmann, Gunnar von Heijne

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins. Nilsson et al. present an integrated approach to the study of cotranslational protein folding, in which the folding transition is mapped by arrest-peptide-mediated force measurements, molecular dynamics simulations, and cryo-EM (electron microscopy). The small zinc-finger domain ADR1a is shown to fold deep inside the ribosome exit tunnel.

Original languageEnglish (US)
Pages (from-to)1533-1540
Number of pages8
JournalCell Reports
Volume12
Issue number10
DOIs
StatePublished - Sep 8 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Nilsson, O. B., Hedman, R., Marino, J., Wickles, S., Bischoff, L., Johansson, M., Müller-Lucks, A., Trovato, F., Puglisi, J. D., O'Brien, E. P., Beckmann, R., & von Heijne, G. (2015). Cotranslational Protein Folding inside the Ribosome Exit Tunnel. Cell Reports, 12(10), 1533-1540. https://doi.org/10.1016/j.celrep.2015.07.065