Altered Phase Diagram Due to a Single Point Mutation in Human GammaD-crystallin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Oct 10

PMID 17923670

Citations 39

Authors

Jennifer J McManus

Aleksey Lomakin

Olutayo Ogun

Ajay Pande

Markus Basan

Jayanti Pande

George B Benedek

Affiliations

Soon will be listed here.

Abstract

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.

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