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    Altered phase diagram due to a single point mutation in human gammaD-crystallin


    McManus, Jennifer J. and Lomakin, Aleksey and Ogun, Olutayo and Pande, Ajay and Basan, Markus and Pande, Jayanti and Benedek, George B. (2007) Altered phase diagram due to a single point mutation in human gammaD-crystallin. Proceedings of the National Academy of Sciences, 104 (43). pp. 16856-16861. ISSN 1091-6490

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    Abstract

    The P23T mutant of human γD-crystallin (HGD) is associated with cataract. We have previously investigated the solution properties of this mutant, as well as those of the closely related P23V and P23S mutants, and shown that although mutations at site 23 of HGD do not produce a significant structural change in the protein, they nevertheless profoundly alter the solubility of the protein. Remarkably, the solubility of the mutants decreases with increasing temperature, in sharp contrast to the behavior of the native protein. This inverted solubility corresponds to a strong increase in the binding energy with temperature. Here we have investigated the liquid–liquid coexistence curve and the diffusivity of the P23V mutant and find that these solution properties are unaffected by the mutation. This means that the chemical potentials in the solution phase are essentially unaltered. The apparent discrepancy between the interaction energies in the solution phase, as compared with the solid phase, is explicable in terms of highly anisotropic interprotein interactions, which are averaged out in the solution phase but are fully engaged in the solid phase.

    Item Type: Article
    Keywords: cataract; lens; protein phase diagram; quasielastic light scattering;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 7896
    Identification Number: https://doi.org/10.1073/pnas.0707412104
    Depositing User: Jennifer McManus
    Date Deposited: 10 Feb 2017 15:45
    Journal or Publication Title: Proceedings of the National Academy of Sciences
    Publisher: National Academy of Sciences
    Refereed: Yes
    URI:

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