{Reference Type}: Journal Article
{Title}: NMR study of the cataract-linked P23T mutant of human gammaD-crystallin shows minor changes in hydrophobic patches that reflect its retrograde solubility.
{Author}: Pande A;Zhang J;Banerjee PR;Puttamadappa SS;Shekhtman A;Pande J;
{Journal}: Biochem Biophys Res Commun
{Volume}: 382
{Issue}: 1
{Year}: Apr 2009 24
{Factor}: 3.322
{DOI}: 10.1016/j.bbrc.2009.03.007
{Abstract}: The Pro23 to Thr (P23T) mutation in human gammaD-crystallin (HGD) shows several cataract phenotypes. We found earlier [A. Pande, O. Annunziata, N. Asherie, O. Ogun, G.B. Benedek, J. Pande, Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin, Biochemistry 44 (2005) 2491-2500] that the mutation dramatically lowers the solubility of P23T but the overall protein fold is maintained. Recently we observed that solutions of P23T showed liquid-liquid phase transition behavior similar to that of HGD but the liquid-protein crystal phase transition was altered, suggesting an asymmetric distribution of "sticky" patches on the protein surface [J.J. McManus, A. Lomakin, O. Ogun, A. Pande, M. Basan, J. Pande, G.B. Benedek, Altered phase diagram due to a single point mutation in human gammaD-crystallin, Proc. Natl. Acad. Sci. USA 104 (2007) 16856-16861]. Here we present high-resolution NMR studies of HGD and P23T in which we have made nearly complete backbone assignments. The data provide a structural basis for explaining the retrograde solubility of P23T by (a) identifying possible "sticky" patches on the surface of P23T and (b) highlighting their asymmetric distribution.