Symport and antiport mechanisms of human glutamate transporters. Academic Article uri icon

Overview

abstract

  • Excitatory amino acid transporters (EAATs) uptake glutamate into glial cells and neurons. EAATs achieve million-fold transmitter gradients by symporting it with three sodium ions and a proton, and countertransporting a potassium ion via an elevator mechanism. Despite the availability of structures, the symport and antiport mechanisms still need to be clarified. We report high-resolution cryo-EM structures of human EAAT3 bound to the neurotransmitter glutamate with symported ions, potassium ions, sodium ions alone, or without ligands. We show that an evolutionarily conserved occluded translocation intermediate has a dramatically higher affinity for the neurotransmitter and the countertransported potassium ion than outward- or inward-facing transporters and plays a crucial role in ion coupling. We propose a comprehensive ion coupling mechanism involving a choreographed interplay between bound solutes, conformations of conserved amino acid motifs, and movements of the gating hairpin and the substrate-binding domain.

publication date

  • May 4, 2023

Research

keywords

  • Amino Acid Transport System X-AG
  • Glutamic Acid

Identity

PubMed Central ID

  • PMC10160106

Scopus Document Identifier

  • 85157973774

Digital Object Identifier (DOI)

  • 10.1016/j.jmb.2007.05.022

PubMed ID

  • 37142617

Additional Document Info

volume

  • 14

issue

  • 1