8afa

Cryo-EM structure of a substrate-bound glutamate transporter homologue GltTk encapsulated within a nanodisc

spinqualitylabelsall models 8afa, resolution 3.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8afa is a 3 chain structure with sequence from Thermococcus kodakarensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.25Å Ligands: ASP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5JID0_THEKO Publication Abstract from PubMed Episodic ataxias (EAs) are rare neurological conditions affecting the nervous system and typically leading to motor impairment. EA6 is linked to the mutation of a highly conserved proline into an arginine in the glutamate transporter EAAT1. In vitro studies showed that this mutation leads to a reduction in the substrates transport and an increase in the anion conductance. It was hypothesised that the structural basis of these opposed functional effects might be the straightening of transmembrane helix 5, which is kinked in the wild-type protein. In this study, we present the functional and structural implications of the mutation P208R in the archaeal homologue of glutamate transporters Glt(Tk). We show that also in Glt(Tk) the P208R mutation leads to reduced aspartate transport activity and increased anion conductance, however a cryo-EM structure reveals that the kink is preserved. The arginine side chain of the mutant points towards the lipidic environment, where it may engage in interactions with the phospholipids, thereby potentially interfering with the transport cycle and contributing to stabilisation of an anion conducting state. Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6.,Colucci E, Anshari ZR, Patino-Ruiz MF, Nemchinova M, Whittaker J, Slotboom DJ, Guskov A Nat Commun. 2023 Mar 31;14(1):1799. doi: 10.1038/s41467-023-37503-y. PMID:37002226 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Symporter 3D structures

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