Abstract
We have used native state exchange to examine the energy landscape of the well-characterized protein T4 lysozyme. Although the protein exhibits two-state behavior by traditional probes, the energy landscape determined here is much more complex. The average stability of the C-terminal subdomain is significantly higher than that for the N-terminus suggesting at least two regions of unfolding. At a more detailed level, there appears to be a broad continuum of stabilities throughout each region. The overall subdomain hierarchy of energies does not mirror data on the folding pathway for this protein, challenging the relationship between energy landscapes and folding trajectories.
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Acknowledgements
We thank K. Fischer, I. Griswold, J. Hollien, G. Lazar, and M.J. Parker for discussion and critical reading of the manuscript. We also thank A.J. Wand and E. Fuentes for discussion about data analysis. This work was supported by grants from the National Institutes of Health (S.M. and F.W.D.) and the W. M. Keck Foundation. M.L. was supported by an NIH Molecular Biophysics Training Grant and B.G. was supported by a Department of Health and Human Services, National Research Service Award.
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Llinás, M., Gillespie, B., Dahlquist, F. et al. The energetics of T4 lysozyme reveal a hierarchy of conformations. Nat Struct Mol Biol 6, 1072–1078 (1999). https://doi.org/10.1038/14956
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DOI: https://doi.org/10.1038/14956
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