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Folding zones inside the ribosomal exit tunnel

Nature Structural & Molecular Biology volume 12, pages 1123–1129 (2005)Cite this article

Abstract

Helicity of membrane proteins can be manifested inside the ribosome tunnel, but the determinants of compact structure formation inside the tunnel are largely unexplored. Using an extended nascent peptide as a molecular tape measure of the ribosomal tunnel, we have previously demonstrated helix formation inside the tunnel. Here, we introduce a series of consecutive polyalanines into different regions of the tape measure to monitor the formation of compact structure in the nascent peptide. We find that the formation of compact structure of the polyalanine sequence depends on its location. Calculation of free energies for the equilibria between folded and unfolded nascent peptides in different regions of the tunnel shows that there are zones of secondary structure formation inside the ribosomal exit tunnel. These zones may have an active role in nascent-chain compaction.

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Figure 1: The tape measure and substituted polyalanines.
Figure 2: Time course of pegylation.
Figure 3: Fraction of peptide compacted, Fc, calculated using data similar to and including those in Figure 2.
Figure 4: Ala5 chimeras and Gly5 substitutions.
Figure 5: Ribosome contribution to secondary structure folding.

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Acknowledgements

We thank S.W. Englander, L. Mayne and R. Horn for helpful discussions and insights. We thank S. White, R. Horn, A. Kosolapov and J. Lear for critical reading of the manuscript. This work was supported by US National Institutes of Health Grant GM 52302.

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  1. Department of Physiology, University of Pennsylvania, Philadelphia, 19104-6085, Pennsylvania, USA

    Jianli Lu & Carol Deutsch

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  1. Jianli Lu
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Correspondence to Carol Deutsch.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Pegylated Cys64 tape measure is ribosome-attached (PDF 93 kb)

Supplementary Table 1

Final extents and rate constants of alanine-containing peptides. (DOC 22 kb)

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Lu, J., Deutsch, C. Folding zones inside the ribosomal exit tunnel. Nat Struct Mol Biol 12, 1123–1129 (2005). https://doi.org/10.1038/nsmb1021

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