Vesicular acetylcholine transporter (VAChT) and similar transporters of the Major Facilitator Superfamily
Vesicular acetylcholine transporter (VAChT) is also called solute carrier family 18 member 3 (SLC18A3) in vertebrates and uncoordinated protein 17 (unc-17) in Caenorhabditis elegans. It is a glycoprotein involved in acetylcholine transport into synaptic vesicles and is responsible for the accumulation of acetylcholine into pre-synaptic vesicules of cholinergic neurons. Variants in SLC18A3 are associated with congenital myasthenic syndrome in humans. VAChT belongs to the bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Feature 1:putative chemical substrate binding pocket [chemical binding site]
Evidence:
Comment:based on the structures of MFS transporters with bound substrates, substrate analogs, and/or inhibitors
Comment:since MFS proteins facilitate the transport of many different substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides, the residues involved in substrate binding may not be strictly conserved among superfamily members
Comment:the substrate binding site or translocation pore has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS transporter
Jiyao W et al.(2023). "The conserved domain database in 2023.",