MURAL - Maynooth University Research Archive Library

    Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a yD-Crystallin Mutant

    Khan, Amir R. and James, Susan and Quinn, Michelle K. and Altan, Irem and Charbonneau, Patrick and McManus, Jennifer J (2019) Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a yD-Crystallin Mutant. Biophysical Journal, 117. pp. 930-937. ISSN 0006-3495

    Download (934kB) | Preview

    Share your research

    Twitter Facebook LinkedIn GooglePlus Email more...

    Add this article to your Mendeley library


    Protein crystal production is a major bottleneck in the structural characterization of proteins. To advance beyond large-scale screening, rational strategies for protein crystallization are crucial. Understanding how chemical anisotropy (or patchiness) of the protein surface, due to the variety of amino-acid side chains in contact with solvent, contributes to proteinprotein contact formation in the crystal lattice is a major obstacle to predicting and optimizing crystallization. The relative scarcity of sophisticated theoretical models that include sufficient detail to link collective behavior, captured in protein phase diagrams, and molecular-level details, determined from high-resolution structural information, is a further barrier. Here, we present two crystal structures for the P23T þ R36S mutant of gD-crystallin, each with opposite solubility behavior: one melts when heated, the other when cooled. When combined with the protein phase diagram and a tailored patchy particle model, we show that a single temperature-dependent interaction is sufficient to stabilize the inverted solubility crystal. This contact, at the P23T substitution site, relates to a genetic cataract and reveals at a molecular level the origin of the lowered and retrograde solubility of the protein. Our results show that the approach employed here may present a productive strategy for the rationalization of protein crystallization.

    Item Type: Article
    Keywords: Temperature-Dependent Interactions; Normal solubility; Inverted Solubility; yD-Crystallin Mutant;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 13459
    Identification Number:
    Depositing User: IR Editor
    Date Deposited: 28 Oct 2020 10:58
    Journal or Publication Title: Biophysical Journal
    Publisher: Cell Press
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

    Repository Staff Only(login required)

    View Item Item control page


    Downloads per month over past year

    Origin of downloads