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Universality of supersaturation in protein-fiber formation

Nature Structural & Molecular Biology volume 23, pages 459–461 (2016)Cite this article

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Abstract

The thermodynamics and kinetics of the aggregation of sickle-cell hemoglobin into fibers have been studied in great detail under a wide range of solution conditions. The stability of the fiber is measured by the solubility; the kinetics is characterized by a delay before the appearance of fibers. A review of data in the literature shows that there is no correlation of the delay time with fiber stability and only a weak correlation with the initial protein concentration. There is, however, a striking collapse of all the data onto a single universal curve when the delay time is plotted versus the supersaturation, which is the ratio of the initial protein concentration to the solubility, expressed as activities. Collapse onto the same universal curve is also obtained when using delay times calculated from the double-nucleation theoretical model.

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Figure 1: Relations among delay time and solubility, initial concentration and supersaturation as ratio of activities.
Figure 2: Kinetics of sickle-hemoglobin aggregation and connection to disease pathogenesis.

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Acknowledgements

We thank A. Szabo, E. Henry and J. Hofrichter for discussions and M. Clore for helpful comments on the manuscript. Work by T.C. and W.A.E. was supported by the intramural research program of NIDDK, US National Institutes of Health.

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Authors and Affiliations

  1. Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Troy Cellmer & William A Eaton

  2. Department of Physics, Drexel University, Philadelphia, Pennsylvania, USA

    Frank A Ferrone

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  2. Frank A Ferrone
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T.C., F.A.F. and W.A.E. performed the calculations, analyzed the data and wrote the paper.

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Correspondence to William A Eaton.

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Supplementary Table 1

Data for Figure 1 of main text (XLS 29 kb)

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Cellmer, T., Ferrone, F. & Eaton, W. Universality of supersaturation in protein-fiber formation. Nat Struct Mol Biol 23, 459–461 (2016). https://doi.org/10.1038/nsmb.3197

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