Fig. 5: Conformational changes of G6PC1 and effects of disease-causing mutations.

a–c Schematic diagram depicting the process of induced-fit conformational changes. The binding of substrate induces ECD to move near the membrane. PS, D254 and K263 stabilize the occluded conformation. The substrates and products are shown in a ball-and-stick representation. Different states are colored light blue, pale yellow and light pink for G6PC1^APO, G6PC1^G6P and G6PC1^Pi, respectively. d Distribution of disease-causing mutations in G6PC1. The structure of G6PC1 is shown as cartoon and colored by rainbow. Mutations are shown as spheres and colored by the different classes: orange for the mutations in residues contributing to G6P recognition and hydrolysis (class A); blue for the mutations in the ECD (class B) and pink for the mutations in the TMD (class C). The front view is shown on the left and the side view is exhibited on the right. e Detailed mutations in class A. The relative mutations are labeled with red letters. The residues are shown as sticks, and G6P is depicted in a ball-and-stick representation. f Examples for mutations in class B. The hydrogen bonds are demonstrated as teal dashed lines. The disease-causing mutations are labeled as red letters. g–j Several instances in class C of disease-causing mutations, shown as sticks and labeled with red letters.