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A kinetic explanation for the rearrangement pathway of BPTI folding

Nature Structural Biology volume 2, pages 1123–1130 (1995)Cite this article

Abstract

Bovine pancreatic trypsin inhibitor (BPTI) does not fold by simple sequential formation of its native disulphide bonds. Instead, an initially formed intermediate, termed N', first rearranges to a more stable species in a slow process that requires substantial unfolding. We find that direct oxidation of N' is also inhibited by native structure which slows both the intermolecular step in oxidation—formation of a mixed disulphide bond with the oxidizing agent GSSG—as well as the subsequent intramolecular step. Folding does not occur appreciably by direct oxidation because the high GSSG concentrations required for efficient mixed disulphide formation cause N' to accumulate as a nonproductive, double-mixed disulphide species. The need to unfold previously acquired native structure, observed in the folding of BPTI, may be a common feature of disulphide-linked folding reactions.

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Author notes

  1. Jonathan S. Weissman

    Present address: Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Physics, M.I.T., Nine Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Jonathan S. Weissman

  2. Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, M.I.T., Nine Cambridge Center, Cambridge, Massachusetts, 02142, USA

    Peter S. Kim

Authors
  1. Jonathan S. Weissman
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  2. Peter S. Kim
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Weissman, J., Kim, P. A kinetic explanation for the rearrangement pathway of BPTI folding. Nat Struct Mol Biol 2, 1123–1130 (1995). https://doi.org/10.1038/nsb1295-1123

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