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Protein folding

When ribosomes pick the structure

Nature Chemistry volume 6, pages 378–379 (2014)Cite this article

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Anfinsen's principle tells us that the folded structure of a protein is determined solely by its sequence. Now, it has been shown that the rate at which a polypeptide chain is synthesized in the cell can affect which of two alternative folded structures it adopts.

Most proteins must fold into three-dimensional structures to reach their biologically active states. In Anfinsen's classic experiment, the protein ribonuclease A was unfolded by chemical denaturants but was then observed to spontaneously refold into the same structure after their removal1. Thus, it was concluded that all the information required for a protein to adopt its folded three-dimensional structure is encoded in its amino acid sequence. However, protein folding in the cell is modulated by many factors that are absent in the test tube, such as molecular crowding and the presence of molecular chaperones2. Moreover, many proteins fold co-translationally, that is, as they are being synthesized on the ribosome3. So whereas in Anfinsen's test tube, folding occurs from the full-length, unfolded polypeptide chain, in the cell N-terminal regions of the polypeptide chain will be available to fold before the C-terminal regions have even been synthesized.

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Figure 1: Protein folding scenarios described by Clark and co-workers4 for polypeptide YKB.

References

  1. Anfinsen, C. B. Science 181, 223–30 (1973).

    Article  CAS  Google Scholar 

  2. Gershenson, A. & Gierasch, L. M. Curr. Opin. Struct. Biol. 21, 32–41 (2011).

    Article  CAS  Google Scholar 

  3. Gloge, F., Becker, A. H., Kramer, G. & Bukau, B. Curr. Opin. Struct. Biol. 24, 24–33 (2014).

    Article  CAS  Google Scholar 

  4. Sander, I. M., Chaney, J. L. & Clark, P. L. J. Am. Chem. Soc. 136, 858–61 (2014).

    Article  CAS  Google Scholar 

  5. Zhang, G. & Ignatova, Z. Curr. Opin. Struct. Biol. 21, 25–31 (2011).

    Article  Google Scholar 

  6. Pechmann, S., Willmund, F. & Frydman, J. Mol. Cell 49, 411–21 (2013).

    Article  CAS  Google Scholar 

  7. Cabrita, L. D., Hsu, S. T., Launay, H., Dobson, C. M. & Christodoulou, J. Proc. Natl Acad. Sci. USA 106, 22239–44 (2009).

    Article  CAS  Google Scholar 

  8. Ebbinghaus, S., Dhar, A., McDonald, J. D. & Gruebele, M. Nature Methods 7, 319–23 (2010).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Elin M. Sivertsson and Laura S. Itzhaki are in the Department of Pharmacology at the University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK,

    Elin M. Sivertsson & Laura S. Itzhaki

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  1. Elin M. Sivertsson
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  2. Laura S. Itzhaki
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Correspondence to Laura S. Itzhaki.

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Sivertsson, E., Itzhaki, L. When ribosomes pick the structure. Nature Chem 6, 378–379 (2014). https://doi.org/10.1038/nchem.1926

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