6WYJ
Cryo-EM structure of the GltPh L152C-G321C mutant in the intermediate state
Summary for 6WYJ
| Entry DOI | 10.2210/pdb6wyj/pdb |
| EMDB information | 21966 |
| Descriptor | Glutamate transporter homolog, ASPARTIC ACID (2 entities in total) |
| Functional Keywords | glutamate transporter homolog gltph, transport protein |
| Biological source | Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3) |
| Total number of polymer chains | 1 |
| Total formula weight | 44718.14 |
| Authors | Font, J.,Chen, I.,Sobti, M.,Stewart, A.G.,Ryan, R.M. (deposition date: 2020-05-13, release date: 2021-02-17, Last modification date: 2024-03-06) |
| Primary citation | Chen, I.,Pant, S.,Wu, Q.,Cater, R.J.,Sobti, M.,Vandenberg, R.J.,Stewart, A.G.,Tajkhorshid, E.,Font, J.,Ryan, R.M. Glutamate transporters have a chloride channel with two hydrophobic gates. Nature, 591:327-331, 2021 Cited by PubMed Abstract: Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity. The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism. Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport. However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family. PubMed: 33597752DOI: 10.1038/s41586-021-03240-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.7 Å) |
Structure validation
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