Send to

Choose Destination
Biophys J. 2019 Sep 3;117(5):930-937. doi: 10.1016/j.bpj.2019.07.019. Epub 2019 Jul 19.

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

Author information

School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Department of Chemistry, Maynooth University, Maynooth, Ireland.
Department of Chemistry, Duke University, Durham, North Carolina.
Department of Chemistry, Maynooth University, Maynooth, Ireland. Electronic address:


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 protein-protein 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 + R36S mutant of γD-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.

[Available on 2020-09-03]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center