7ahk

Crystal structure of the outward-facing state of the substrate-free Na+-only bound glutamate transporter homolog GltPhCrystal structure of the outward-facing state of the substrate-free Na+-only bound glutamate transporter homolog GltPh

Structural highlights 7ahk is a 1 chain structure with sequence from Pyrococcus horikoshii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: , , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLT_PYRHO Sodium-dependent, high-affinity amino acid transporter that mediates aspartate uptake (PubMed:17435767, PubMed:19380583, PubMed:17230192, Ref.11). Has only very low glutamate transport activity (PubMed:19380583, PubMed:17230192). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions, resulting in electrogenic transport (PubMed:17435767, PubMed:19380583, Ref.11). Na(+) binding enhances the affinity for aspartate (PubMed:19380583, Ref.11). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:17435767). In contrast to mammalian homologs, transport does not depend on pH or K(+) ions (PubMed:19380583). [PDB:4P19] Publication Abstract from PubMed Excitatory amino acid transporters (EAATs) harness [Na(+)], [K(+)], and [H(+)] gradients for fast and efficient glutamate removal from the synaptic cleft. Since each glutamate is cotransported with three Na(+) ions, [Na(+)] gradients are the predominant driving force for glutamate uptake. We combined all-atom molecular dynamics simulations, fluorescence spectroscopy, and x-ray crystallography to study Na(+):substrate coupling in the EAAT homolog Glt(Ph) A lipidic cubic phase x-ray crystal structure of wild-type, Na(+)-only bound Glt(Ph) at 2.5-A resolution revealed the fully open, outward-facing state primed for subsequent substrate binding. Simulations and kinetic experiments established that only the binding of two Na(+) ions to the Na1 and Na3 sites ensures complete HP2 gate opening via a conformational selection-like mechanism and enables high-affinity substrate binding via electrostatic attraction. The combination of Na(+)-stabilized gate opening and electrostatic coupling of aspartate to Na(+) binding provides a constant Na(+):substrate transport stoichiometry over a broad range of neurotransmitter concentrations. Na(+)-dependent gate dynamics and electrostatic attraction ensure substrate coupling in glutamate transporters.,Alleva C, Kovalev K, Astashkin R, Berndt MI, Baeken C, Balandin T, Gordeliy V, Fahlke C, Machtens JP Sci Adv. 2020 Nov 18;6(47):eaba9854. doi: 10.1126/sciadv.aba9854. Print 2020 Nov. PMID:33208356 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Symporter 3D structures

spinqualitylabelsall models 7ahk, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image