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TitleIon transport and regulation in a synaptic vesicle glutamate transporter.
Journal, issue, pagesScience, Vol. 368, Issue 6493, Page 893-897, Year 2020
Publish dateMay 22, 2020
AuthorsFei Li / Jacob Eriksen / Janet Finer-Moore / Roger Chang / Phuong Nguyen / Alisa Bowen / Alexander Myasnikov / Zanlin Yu / David Bulkley / Yifan Cheng / Robert H Edwards / Robert M Stroud /
PubMed AbstractSynaptic vesicles accumulate neurotransmitters, enabling the quantal release by exocytosis that underlies synaptic transmission. Specific neurotransmitter transporters are responsible for this ...Synaptic vesicles accumulate neurotransmitters, enabling the quantal release by exocytosis that underlies synaptic transmission. Specific neurotransmitter transporters are responsible for this activity and therefore are essential for brain function. The vesicular glutamate transporters (VGLUTs) concentrate the principal excitatory neurotransmitter glutamate into synaptic vesicles, driven by membrane potential. However, the mechanism by which they do so remains poorly understood owing to a lack of structural information. We report the cryo-electron microscopy structure of rat VGLUT2 at 3.8-angstrom resolution and propose structure-based mechanisms for substrate recognition and allosteric activation by low pH and chloride. A potential permeation pathway for chloride intersects with the glutamate binding site. These results demonstrate how the activity of VGLUTs can be coordinated with large shifts in proton and chloride concentrations during the synaptic vesicle cycle to ensure normal synaptic transmission.
External linksScience / PubMed:32439795 / PubMed Central
MethodsEM (single particle)
Resolution3.8 Å
Structure data

21040

8sbe

EMDB-21040: Structure of the rat vesicular glutamate transporter 2 determined by single particle Cryo-EM
PDB-8sbe: Structure of the rat vesicular glutamate transporter 2 determined by single-particle Cryo-EM
Method: EM (single particle) / Resolution: 3.8 Å

Source
  • rattus norvegicus (Norway rat)
KeywordsMEMBRANE PROTEIN / glutamate transport / synaptic vesicle / Major facilitator Superfamily / excitatory neurotransmission

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