Extended Data Fig. 9: Sugar binding site in SLC37A2 and structural mapping of the SLC37A4 mutations related to human GSD-Ib disease.
From: Structural basis of glucose-6-phosphate transport by human SLC37A2
a, Sugar binding site in SLC37A2 and the sugar transporter homologues of the MFS superfamily. The N-domain and C-domain of SLC37A2 and the sugar transporter homologues are in different colours. The bound G6P and glucose (Glc) molecules are shown in sticks. The PDB accession codes are indicated for the homologue structures. b, Structural superposition of glucose-bound human GLUT3 (hGLUT3) and G6P-bound SLC37A2. c, Missense mutations in SLC37A4 that cause human GSD-Ib disease mapped to the predicted SLC37A4 structure using AlphaFold2 and the corresponding mutations in the determined G6P-bound SLC37A2 structure. Mutations are shown in slate spheres. Conserved sites within SLC37A4 and SLC37A2 are coloured white. Conserved sites involved in G6P binding in SLC37A2G6P, CO are coloured red. d, 3H-G6P transport by SLC37A2WT and selected mutants corresponding to those in SLC37A4 which are associated with GSD-Ib disease. Net 3H-G6P accumulations of the mutants calculated by deleting the 3H-G6P accumulation of the control group were normalized to the net accumulation of SLC37A2WT. Data are means ± SD (n = 3 biologically independent repeats). Significances of the mutants versus wild-type (WT) were evaluated using one-way ANOVA with Dunnett’s multiple comparisons test. **** P < 0.0001. e, Side-view of the mutations corresponding to those disease-related residues in SLC37A2 near the G6P binding site in SLC37A2G6P, CO. f, Top-view of the mutations corresponding to those disease-related residues in SLC37A2 near the G6P binding site in SLC37A2G6P, CO. g, G403 residue in the SLC37A2 luminal- and cytosolic-open conformations.
