Altered phase diagram due to a single point mutation in human gammaD-crystallin.
The P23T mutant of human gammaD-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.
McManus
Jennifer J
JJ
Materials Processing Center, Department of Physics, and Center for Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Lomakin
Aleksey
A
Ogun
Olutayo
O
Pande
Ajay
A
Basan
Markus
M
Pande
Jayanti
J
Benedek
George B
GB
D003459:Crystallins / Q000737:chemistry* / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008027:Light; D008859:Microscopy, Polarization; D008954:Models, Biological; D044367:Phase Transition; D017354:Point Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics; D020836:Protein Structure, Quaternary; D012542:Scattering, Radiation; D012995:Solubility; D013696:Temperature; D014633:Valine / Q000235:genetics; D038222:gamma-Crystallins
C504903:CRYGD protein, human; D003459:Crystallins; D006451:Hemoglobin, Sickle; D038222:gamma-Crystallins; D011392:Proline; D014633:Valine