FIGURE 5.

Effects of human disease mutations on PDZ2+²⁷⁰ structure and stability. A, the structure of wild type PDZ2+²⁷⁰ shown with a hydrogen bond formed between positively charged guanidinium group of Arg¹⁵³ and the negatively charged carboxylate group of Asp²³² and Asp¹⁹⁷. Residues with weighted backbone chemical shift difference greater than 0.1 ppm of mutant R153Q with reference to wild-type PDZ2+²⁷⁰ (supplemental Fig. S4C) are painted yellow. B, in wild type PDZ2+²⁷⁰, the negatively charged Glu²²⁵ is complemented by the positive charge of Lys¹⁵⁸ and Lys²²⁷. C, overlay of ¹⁵N HSQC of PDZ2+²⁷⁰ (red) and mutant R153Q (black) at 30 °C. D, thermal unfolding curves of mutant R153Q (red) and wild-type PDZ2+²⁷⁰ (black) monitored by CD. The molar ellipticity (y axis) as a function of temperature (x axis) was fitted to a standard two-state unfolding equation.