Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Nat Commun. 2024 Aug 2;15(1):6511. doi: 10.1038/s41467-024-50934-5.
Vesicular monoamine transporter 2 (VMAT2) belongs to the major facilitator superfamily (MFS), and mediates cytoplasmic monoamine packaging into presynaptic vesicles. Here, we present two cryo-EM structures of VMAT2, with a frog VMAT2 adopting a canonical MFS fold and an engineered sheep VMAT2 adopting a non-canonical fold. Both VMAT2 proteins mediate uptake of a selective fluorescent VMAT2 substrate into cells. Molecular docking, substrate binding and transport analysis reveal potential substrate binding mechanism in VMAT2. Meanwhile, caution is advised when interpreting engineered membrane protein structures.
囊泡单胺转运体 2（VMAT2）属于主要协助超家族（MFS），介导细胞质单胺包装到突触前囊泡中。在这里，我们展示了两个 VMAT2 的冷冻电镜结构，一个青蛙 VMAT2 采用典型的 MFS 折叠，一个工程化的绵羊 VMAT2 采用非典型的折叠。两种 VMAT2 蛋白都介导选择性荧光 VMAT2 底物进入细胞的摄取。分子对接、底物结合和转运分析揭示了 VMAT2 中的潜在底物结合机制。同时，在解释工程化膜蛋白结构时需要谨慎。
