Abstract
Although tertiary folding of whole protein domains is prohibited by the cramped dimensions of the ribosomal tunnel, dynamic tertiary interactions may permit folding of small elementary units within the tunnel. To probe this possibility, we used a β-hairpin and an α-helical hairpin from the cytosolic N terminus of a voltage-gated potassium channel and determined a probability of folding for each at defined locations inside and outside the tunnel. Minimalist tertiary structures can form near the exit port of the tunnel, a region that provides an entropic window for initial exploration of local peptide conformations. Tertiary subdomains of the nascent peptide fold sequentially, but not independently, during translation. These studies offer an approach for diagnosing the molecular basis for folding defects that lead to protein malfunction and provide insight into the role of the ribosome during early potassium channel biogenesis.
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Acknowledgements
We thank R. Horn, J. Frank and U. Hartl for careful reading of the manuscript and R. Horn for helpful discussion. This research was funded by the US National Institutes of Health grant GM 52302 to C.D.
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A.K. performed the experiments; A.K. and C.D. designed the research, interpreted the results and wrote the manuscript.
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Supplementary Figures 1–4, Supplementary Table 1 and Supplementary Results (PDF 333 kb)
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Kosolapov, A., Deutsch, C. Tertiary interactions within the ribosomal exit tunnel. Nat Struct Mol Biol 16, 405–411 (2009). https://doi.org/10.1038/nsmb.1571
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DOI: https://doi.org/10.1038/nsmb.1571
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