TY - JOUR
T1 - Altered phase diagram due to a single point mutation in human γD-crystallin
AU - McManus, Jennifer J.
AU - Lomakin, Aleksey
AU - Ogun, Olutayo
AU - Pande, Ajay
AU - Basan, Markus
AU - Pande, Jayanti
AU - Benedek, George B.
PY - 2007/10/23
Y1 - 2007/10/23
N2 - 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.
AB - 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.
KW - Cataract
KW - Lens
KW - Protein phase diagram
KW - Quasielastic light scattering
UR - http://www.scopus.com/inward/record.url?scp=36749055226&partnerID=8YFLogxK
U2 - 10.1073/pnas.0707412104
DO - 10.1073/pnas.0707412104
M3 - Article (Academic Journal)
C2 - 17923670
AN - SCOPUS:36749055226
SN - 0027-8424
VL - 104
SP - 16856
EP - 16861
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 43
ER -