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

Jennifer J. McManus, Aleksey Lomakin, Olutayo Ogun, Ajay Pande, Markus Basan, Jayanti Pande, George B. Benedek*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

88 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)16856-16861
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
Publication statusPublished - 23 Oct 2007


  • Cataract
  • Lens
  • Protein phase diagram
  • Quasielastic light scattering


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