Figure 7: Missense mutations in the N- and C-terminal domains of citrin causing citrin deficiency.

(a) Six missense mutations found in the N-terminal domain of citrin. The overall structure of the regulatory domain of citrin is depicted and is coloured according to Fig. 1a. The residues of the missense mutations are depicted in sphere representation. Bound calcium ions are shown as green spheres. (b) Key interactions within EF-hand 1 and with the C-terminal helix near Ala25. Residues forming key interactions are shown in stick representation. EF-hand 1 and the C-terminal helix are shown in purple and wheat, respectively. A water molecule mediating an interaction between EF-hand 1 and the C-terminal helix is shown as a blue sphere. Ala25 is shown in a yellow stick representation. (c) Interaction of Tyr148 with the conserved Asp89. Tyr148 and Asp89 are shown in stick representation and coloured in yellow and cyan, respectively. (d) Interaction of Glu252 with conserved Thr250. Glu252 and Thr250 are shown in stick representation and coloured in yellow and orange, respectively. Hydrogen bond interactions are shown as black-dotted lines.