8XTX

structure of a protein

Summary for 8XTX

• Entry DOI: 10.2210/pdb8xtx/pdb
• EMDB information: 38652
• Descriptor: Green fluorescent protein,Vesicular acetylcholine transporter,antibody (1 entity in total)
• Functional Keywords: transporter, membrane protein, transport protein
• Biological source: Aequorea victoria; More
• Total number of polymer chains: 1
• Total formula weight: 89562.81

Authors

Zhao, Y.,Ma, Q.,Dong, Y.,Meng, Y. (deposition date: 2024-01-12, release date: 2024-12-25, Last modification date: 2025-06-11)

Primary citation

Ma, Q.,Ma, K.,Dong, Y.,Meng, Y.,Zhao, J.,Li, R.,Bai, Q.,Wu, D.,Jiang, D.,Sun, J.,Zhao, Y.
Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT.
Nat.Struct.Mol.Biol., 32:818-827, 2025

PubMed Abstract: The vesicular acetylcholine transporter (VAChT) has a pivotal role in packaging and transporting acetylcholine for exocytotic release, serving as a vital component of cholinergic neurotransmission. Dysregulation of its function can result in neurological disorders. It also serves as a target for developing radiotracers to quantify cholinergic neuron deficits in neurodegenerative conditions. Here we unveil the cryo-electron microscopy structures of human VAChT in its apo state, the substrate acetylcholine-bound state and the inhibitor vesamicol-bound state. These structures assume a lumen-facing conformation, offering a clear depiction of architecture of VAChT. The acetylcholine-bound structure provides a detailed understanding of how VAChT recognizes its substrate, shedding light on the coupling mechanism of protonation and substrate binding. Meanwhile, the vesamicol-bound structure reveals the binding mode of vesamicol to VAChT, laying the structural foundation for the design of the next generation of radioligands targeting VAChT.

PubMed: 39806024
DOI: 10.1038/s41594-024-01462-9

Experimental method

ELECTRON MICROSCOPY (3.4 Å)