Extended Data Fig. 9: Structural comparison between VAChT and VMAT2 in different conformations.

a-c. Superposition of the overall structures of VAChT^VES (purple and pink) and VMAT2^RES (light blue) viewed parallel to the membrane plane (a), from the luminal side (b), and cytoplasmic side (c). The N-domain shown in cartoon is used as a reference for structural superposition. C-domains are shown as cylinders and an approximate 32-degree rotation between the two structures is indicated by black arrows. d-f. Superposition of the overall structures of VAChT^VES (purple and pink) and VMAT2^KET (pale cyan, PDB ID: 8JT9) shown in cylinders, viewed parallel to the membrane plane (d). The cytoplasmic gates are outlined by a black dashed circle. The critical residues and salt bridges involved in forming the gate of VAChT^VES (e) and VMAT2^KET (f) are depicted in sticks and black dashed lines, respectively. g-i. Superposition of the overall structures of VAChT^Cyto shown in cylinders (purple and pink, cytoplasm-facing model of VAChT) and VMAT2^RES (pale cyan). The luminal gates are outlined by a black dashed circle. The critical residues and salt bridges involved in forming the gate of VAChT^Cyto (e) and VMAT2^RES (f) are depicted in sticks and black dashed lines, respectively.