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A green light for protein folding

Nature Biotechnology volume 17, pages 637–638 (1999)Cite this article

Studies of the cellular environment have revealed that an extensive battery of chaperonins, isomerases, and other helper proteins are required for efficient protein folding in cells. It is becoming increasingly clear that for efficient protein folding and assembly, a substantial fraction of proteins normally access some form of helper3.

Given this complexity, it is not surprising that, as so many researchers have painfully learned, efficient polypeptide chain translation in bacteria does not automatically lead to correctly folded proteins. Instead, folding intermediates polymerize into the kinetically trapped inclusion body state4, and recovering active proteins requires solubilization and refolding in vitro. This can be further complicated by the tendency for the competing off-pathway self-association reactions of folding intermediates to plague in vitro refolding reactions, requiring considerable time and effort to find productive refolding conditions. Although this problem is generally solvable in biotechnology firms with experienced and properly trained staffs, it can be a considerable barrier in a research laboratory where the protein is being expressed for its initial characterization or structure determination.

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Figure 1: Polypeptide chains failing to fold productively in E. coli or other cells frequently end up in the aggregated inclusion body state, seen here in an electron micrograph of a thin section of E. coli overexpressing a recombinant protein (S. Betts and P. Reilly, unpublished data).

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Authors and Affiliations

  1. professor, department of biology, Massachusetts Institute of Technology, Cambridge, 02139-4307 , MA

    Jonathan King

  2. postdoctoral associate, department of biology, Massachusetts Institute of Technology, Cambridge, 02139-4307 , MA

    Scott Betts

Authors
  1. Jonathan King
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  2. Scott Betts
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King, J., Betts, S. A green light for protein folding. Nat Biotechnol 17, 637–638 (1999). https://doi.org/10.1038/10848

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