{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ye J"],"funding":["National Institute of Neurological Disorders and Stroke","National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases","NIAID NIH HHS","NHLBI NIH HHS","Children's Discovery Institute","American Heart Association Inc","National Heart Lung and Blood Institute","National Institute of General Medical Sciences","Lundbeck Foundation","National Institute of Allergy and Infectious Diseases","Hormel Foundation Inc","University of Minnesota","NINDS NIH HHS","NIGMS NIH HHS","W M Keck Foundation"],"pagination":["116490"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12721464"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["44(11)"],"pubmed_abstract":["Vesicular monoamine transporter 2 (VMAT2) stores monoamine neurotransmitters in synaptic vesicles to regulate their release. VMAT2 is a primary target in neurological disorder treatment and contributes to amphetamine-induced psychostimulation. Here, we report cryo-electron microscopy structures of human VMAT2 capturing a cytoplasmic-open state with reserpine and lumenal-facing states with serotonin and histamine in open, amphetamine in less open, tetrabenazine in fully occluded, and unbound VMAT2 in partially occluded conformations. This structural flexibility facilitates tetrabenazine binding and proton-driven monoamine accumulation. VMAT2 binds serotonin and histamine in opposite orientations through two negatively charged sites, one functioning in protonation. Amphetamine binds in the s"],"journal":["Cell reports"],"pubmed_title":["Molecular basis of vesicular monoamine transport and neurological drug interactions."],"pmcid":["PMC12721464"],"funding_grant_id":["R324-2019-1855","R01 GM131008","R01 HL121718","R01 NS092865","R01 AI158500","MCII 2020-854"],"pubmed_authors":["Li W","Ammerman A","Liu B","Chen H","Wang Y","Wang K","Xu J","Ye J"],"additional_accession":[]},"is_claimable":false,"name":"Molecular basis of vesicular monoamine transport and neurological drug interactions.","description":"Vesicular monoamine transporter 2 (VMAT2) stores monoamine neurotransmitters in synaptic vesicles to regulate their release. VMAT2 is a primary target in neurological disorder treatment and contributes to amphetamine-induced psychostimulation. Here, we report cryo-electron microscopy structures of human VMAT2 capturing a cytoplasmic-open state with reserpine and lumenal-facing states with serotonin and histamine in open, amphetamine in less open, tetrabenazine in fully occluded, and unbound VMAT2 in partially occluded conformations. This structural flexibility facilitates tetrabenazine binding and proton-driven monoamine accumulation. VMAT2 binds serotonin and histamine in opposite orientations through two negatively charged sites, one functioning in protonation. Amphetamine binds in the s","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-06T04:48:39.038Z","creation":"2026-05-25T03:12:09.475Z"},"accession":"S-EPMC12721464","cross_references":{"pubmed":["41166311"],"doi":["10.1016/j.celrep.2025.116490"]}}