ArticleProceedings of the National Academy of Sciences of the United States of America2013
Identification of molecular hinge points mediating alternating access in the vesicular monoamine transporter VMAT2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular basis of vesicular monoamine transport and neurological drug interactions.Cell reports · 2025Article
- Binding mechanism and antagonism of the vesicular acetylcholine transporter VAChT.Nature structural & molecular biology · 2025Article
- Drug inhibition and substrate transport mechanisms of human VMAT2.Nature communications · 2025Article
- Neurotransmitter recognition by human vesicular monoamine transporter 2.Nature communications · 2024Article
- Engineering of a mammalian VMAT2 for cryo-EM analysis results in non-canonical protein folding.Nature communications · 2024Article
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- Transport and inhibition mechanisms of human VMAT2.Nature · 2024Article
- Transport and inhibition mechanism for VMAT2-mediated synaptic vesicle loading of monoamines.Cell research · 2024Article
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- Review
- Inhibition of Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily in Bacterial Pathogens.Biomedicines · 2023Review
- The Major Facilitator Superfamily and Antimicrobial Resistance Efflux Pumps of the ESKAPEE PathogenAntibiotics (Basel, Switzerland) · 2023Review
- Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone.Communications biology · 2022Article
- Membrane Efflux Pumps of PathogenicMicroorganisms · 2022Review
- Mutagenesis and functional analysis of SotB: A multidrug transporter of the major facilitator superfamily fromFrontiers in microbiology · 2022Article
- Structures and General Transport Mechanisms by the Major Facilitator Superfamily (MFS).Chemical reviews · 2021Article
- Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps.Microorganisms · 2020Review
- The ins and outs of vesicular monoamine transporters.The Journal of general physiology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Vesicular monoamine transporter 2 (VMAT2) catalyzes transport of monoamines into storage vesicles in a process that involves exchange of the charged monoamine with two protons. VMAT2 is a member of the DHA12 family of multidrug transporters that belongs to the major facilitator superfamily (MFS) of secondary transporters. Here we present a homology model of VMAT2, which has the standard MFS fold, that is, with two domains of six transmembrane helices each which are related by twofold pseudosymmetry and whose axis runs normal to the membrane and between the two halves. Demonstration of the essential role of a membrane-embedded glutamate and confirmation of the existence of a hydrogen bond probably involved in proton transport provide experimental evidence that validates some of the predictions inherent to the model. Moreover, we show the essential role of residues at two anchor points between the two bundles. These residues appear to function as molecular hinge points about which the two six transmembrane-helix bundles flex and straighten to open and close the pathways on either side of the membrane as required for transport. Polar residues that create a hydrogen bond cluster form one of the anchor points of VMAT2. The other results from hydrophobic interactions. Residues at the anchor points are strongly conserved in other MFS transporters in one way or another, suggesting that interactions at these locations will be critical in most, if not all, MFS transporters.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.