Fig. 2: Structure of human XPR1 in the outward-open state.
From: Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate
Cryo-EM maps (a) and structural models (b) of the outward-open state XPR1 (XPR1OUT) from the side view and extracellular view. The two protomers of XPR1, lipids, and InsP6 molecules are colored light pink, light green, magenta, and red, respectively. The densities of the Pi are shown as blue meshes as an insert. Cryo-EM maps (c) and structural models (d) of the closed state XPR1 with SPX (XPR1C_SPX) from the side view and extracellular view. The color schemes are the same as in (a, b). e Structural comparison of XPR1C (cyan) and XPR1OUT (light pink and light green), superimposed based on the TMDs. f Schematic diagram of the secondary structure features of full-length XPR1OUT. The TMD and the SPX domains are presented in gray and pink. The Glu622/Phe623 motif near the C-terminal of XPR1 is labeled in purple. InsP6 is labeled in red. g Schematic diagram of the binding between KIDINS220 (1–432) and XPR1 in the outward-open state conformation. The XPR1OUT atomic model was superimposed into the XPR1OUT state density map after an additional two rounds of 3D classification at a low counter level. The two protomers of XPR1. and InsP6 molecules are presented in light pink, light green, and red, respectively. The cryo-EM density maps of XPR1 and KIDINS220 at low counter level are shown in transparent mode and colored gray and orange, respectively. The binding pattern is based on the Alphafold2 prediction result presented in Supplementary Fig. 1a, b. h Superimposition of our XPR1OUT structure with the previously reported XPR1-SPX-1,5-InsP8 crystal structure by aligning one of the SPX domains. The InsP6 molecules and the protomer of XPR1OUT_A were colored in light pink and the protomer of XPR1OUT_B in light green. The InsP8 molecule and the SPXA protomer of the XPR1-SPX-1,5-InsP8 complex were colored in dark blue, and the SPXB protomer in light blue.
