Fig. 4: LAT1 bound to BCH in the occluded conformation.

a Close-up view of BCH modeled into the cryo-EM map. b Cut-away surface representation of LAT1, showing that BCH is occluded from both sides of the membrane. c Interaction of BCH with the surrounding residues. Dotted lines depict hydrogen bonds. d, e Comparison of JPH203- and BCH-binding sites of LAT1. The ligands and important residues are shown as sticks and spheres. f Rotation of Phe400 from the JPH203-bound (transparent) to BCH-bound (opaque) structures. g cis inhibition assay. Uptake of ʟ-[¹⁴C]Leu into Xenopus oocytes expressing wild-type LAT1 and CD98hc was measured in the presence or absence of indicated compounds in the external solution. As a control, water was injected instead of cRNAs. Data are mean ± SD and each data point represents a single oocyte (n = 7 for 1 μM JPH203; n = 8 for 0 μM JPH203 and 500 μM BCH; and n = 10 for Water). h Counterflow assay to evaluate substrate-induced antiport. Efflux of pre-loaded ʟ-[¹⁴C]Leu from Xenopus oocytes was measured in the presence or absence of indicated compounds in the external buffer solution. Data are mean ± SD and each data point represents a single oocyte (n = 7 for Leu; n = 9 for buffer and JPH203; and n = 10 for BCH). Source data are available with this paper as Source Data file.