A protein-folding reaction under kinetic control (original) (raw)

Nature volume 356, pages 263–265 (1992)Cite this article

Abstract

SYNTHESIS of α-lytic protease is as a precursor containing a 166 amino-acid pro region1 transiently required for the correct folding of the protease domain2–4. By omitting the pro region in an _in vitro_refolding reaction we trapped an inactive, but folding competent state (I) having an expanded radius yet native-like secondary structure. The I state is stable for weeks at physiological pH in the absence of denaturant, but rapidly folds to the active, native state on addition of the pro region as a separate polypeptide chain. The mechanism of action of the pro region is distinct from that of the chaperonins5,6: rather than reducing the rate of off-pathway reactions, the pro region accelerates the rate-limiting step on the folding pathway by more than 107. Because both the I and native states are stable under identical conditions with no detectable interconversion, the folding of α-lytic protease must be under kinetic and not thermodynamic control.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, The Department of Biochemistry and the Biophysics Graduate Group, University of California at San Francisco, San Francisco, California, 94143-0448, USA
    David Baker, Julie L. Sohl & David A. Agard

Authors

  1. David Baker
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  2. Julie L. Sohl
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  3. David A. Agard
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Baker, D., Sohl, J. & Agard, D. A protein-folding reaction under kinetic control.Nature 356, 263–265 (1992). https://doi.org/10.1038/356263a0

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