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Chain collapse can occur concomitantly with the rate-limiting step in protein folding

Nature Structural Biology volume 6, pages 554–556 (1999)Cite this article

Abstract

We have directly characterized the extent of chain collapse early in the folding of protein L using time-resolved small angle X-ray scattering. We find that, immediately after the initiation of refolding, the protein exhibits dimensions indistinguishable from those observed under highly denaturing, equilibrium conditions and that this expanded initial state collapses with the same rate as that of the overall folding reaction. The observation that chain compaction need not significantly precede the rate-limiting step of folding demonstrates that rapid chain collapse is not an obligatory feature of protein folding reactions.

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Figure 1: The equilibrium unfolding of protein L is accurately described as a two-state process in which only the denatured and native states are populated.
Figure 2: Time-resolved SAXS indicates that the refolding of protein L lacks a burst-phase collapse event under the conditions employed.
Figure 3: A decrease in forward scattering (I0) is observed during folding.
Figure 4: A model of the folding barrier of protein L can be constrained using a number of recent experimental results.

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Acknowledgements

We thank H. Tsuruta for aid with and development of the stopped-flow apparatus used in this study and H. S. Chan, K. Fiebig, W. Parson, D. Shortle, D. Teller and P. Wolynes for critical readings of the manuscript. Data were collected at Beam Line 4-2 of the Stanford Synchrotron Radiation Laboratory (SSRL). The US Department of Energy and the National Institutes of Health support SSRL. A NIH FIRST award and Packard Foundation and NSF young investigator awards to D.B. supported portions of this research.

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  1. Kevin W. Plaxco

    Present address: Department of Chemistry and Interdepartmental Program in Biochemistry and Molecular Biology,

Authors and Affiliations

  1. Department of Biochemistry, University of Washington, Seattle, 98195, Washington, USA

    Kevin W. Plaxco & David Baker

  2. Department of Applied Physics, Stanford University, Stanford, 92343, California, USA

    Ian S. Millett, Daniel J. Segel & Sebastian Doniach

  3. University of California, Santa Barbara, Santa Barbara, California, 93106, USA

    Kevin W. Plaxco

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Correspondence to David Baker.

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Plaxco, K., Millett, I., Segel, D. et al. Chain collapse can occur concomitantly with the rate-limiting step in protein folding. Nat Struct Mol Biol 6, 554–556 (1999). https://doi.org/10.1038/9329

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