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| | <StructureSection load='6wzb' size='340' side='right'caption='[[6wzb]], [[Resolution|resolution]] 3.45Å' scene=''> | | <StructureSection load='6wzb' size='340' side='right'caption='[[6wzb]], [[Resolution|resolution]] 3.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wzb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WZB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wzb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii_OT3 Pyrococcus horikoshii OT3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WZB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PH1295 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=70601 Pyrococcus horikoshii])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6wzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wzb OCA], [https://pdbe.org/6wzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wzb RCSB], [https://www.ebi.ac.uk/pdbsum/6wzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wzb ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6wzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wzb OCA], [https://pdbe.org/6wzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wzb RCSB], [https://www.ebi.ac.uk/pdbsum/6wzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wzb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GLT_PYRHO 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).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19]
| + | [https://www.uniprot.org/uniprot/GLT_PYRHO 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).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pyrococcus horikoshii]] | + | [[Category: Pyrococcus horikoshii OT3]] |
| - | [[Category: Chen, I]] | + | [[Category: Chen I]] |
| - | [[Category: Font, J]] | + | [[Category: Font J]] |
| - | [[Category: Ryan, R]] | + | [[Category: Ryan R]] |
| - | [[Category: Glutamate transporter homolog]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
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).[1] [2] [3] [PDB:4P19]
Publication Abstract from PubMed
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(1). 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(2-5). Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport(6-8). 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.
Glutamate transporters have a chloride channel with two hydrophobic gates.,Chen I, Pant S, Wu Q, Cater RJ, Sobti M, Vandenberg RJ, Stewart AG, Tajkhorshid E, Font J, Ryan RM Nature. 2021 Feb 17. pii: 10.1038/s41586-021-03240-9. doi:, 10.1038/s41586-021-03240-9. PMID:33597752[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Boudker O, Ryan RM, Yernool D, Shimamoto K, Gouaux E. Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature. 2007 Jan 25;445(7126):387-93. Epub 2007 Jan 17. PMID:17230192 doi:10.1038/nature05455
- ↑ Ryan RM, Mindell JA. The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nat Struct Mol Biol. 2007 May;14(5):365-71. doi: 10.1038/nsmb1230. Epub 2007 Apr , 15. PMID:17435767 doi:http://dx.doi.org/10.1038/nsmb1230
- ↑ Ryan RM, Compton EL, Mindell JA. Functional characterization of a Na+-dependent aspartate transporter from Pyrococcus horikoshii. J Biol Chem. 2009 Jun 26;284(26):17540-8. doi: 10.1074/jbc.M109.005926. Epub 2009, Apr 20. PMID:19380583 doi:http://dx.doi.org/10.1074/jbc.M109.005926
- ↑ Chen I, Pant S, Wu Q, Cater RJ, Sobti M, Vandenberg RJ, Stewart AG, Tajkhorshid E, Font J, Ryan RM. Glutamate transporters have a chloride channel with two hydrophobic gates. Nature. 2021 Feb 17. pii: 10.1038/s41586-021-03240-9. doi:, 10.1038/s41586-021-03240-9. PMID:33597752 doi:http://dx.doi.org/10.1038/s41586-021-03240-9
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