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5llu

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Current revision

Structure of the thermostabilized EAAT1 cryst-II mutant in complex with L-ASP

Structural highlights

5llu is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.32Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

EAA1_HUMAN Alternating hemiplegia of childhood;Episodic ataxia type 6. The disease is caused by mutations affecting the gene represented in this entry.

Function

AAAT_HUMAN Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids (PubMed:8702519). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development (PubMed:10708449, PubMed:23492904).^[1] ^[2] ^[3] (Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114.^[4] ^[5] (Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus.^[6] (Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.^[7] EAA1_HUMAN Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.

Publication Abstract from PubMed

Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain and amino acids in peripheral organs. Dysregulation of the function of SLC1 transporters is associated with neurodegenerative disorders and cancer. Here we present crystal structures of a thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1 (EAAT1), with and without allosteric and competitive inhibitors bound. The structures reveal architectural features of the human transporters, such as intra- and extracellular domains that have potential roles in transport function, regulation by lipids and post-translational modifications. The coordination of the allosteric inhibitor in the structures and the change in the transporter dynamics measured by hydrogen-deuterium exchange mass spectrometry reveal a mechanism of inhibition, in which the transporter is locked in the outward-facing states of the transport cycle. Our results provide insights into the molecular mechanisms underlying the function and pharmacology of human SLC1 transporters.

Structure and allosteric inhibition of excitatory amino acid transporter 1.,Canul-Tec JC, Assal R, Cirri E, Legrand P, Brier S, Chamot-Rooke J, Reyes N Nature. 2017 Apr 27;544(7651):446-451. doi: 10.1038/nature22064. Epub 2017 Apr, 19. PMID:28424515^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Blond JL, Lavillette D, Cheynet V, Bouton O, Oriol G, Chapel-Fernandes S, Mandrand B, Mallet F, Cosset FL. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol. 2000 Apr;74(7):3321-9. PMID:10708449
↑ Sugimoto J, Sugimoto M, Bernstein H, Jinno Y, Schust D. A novel human endogenous retroviral protein inhibits cell-cell fusion. Sci Rep. 2013;3:1462. doi: 10.1038/srep01462. PMID:23492904 doi:http://dx.doi.org/10.1038/srep01462
↑ Kekuda R, Prasad PD, Fei YJ, Torres-Zamorano V, Sinha S, Yang-Feng TL, Leibach FH, Ganapathy V. Cloning of the sodium-dependent, broad-scope, neutral amino acid transporter Bo from a human placental choriocarcinoma cell line. J Biol Chem. 1996 Aug 2;271(31):18657-61. PMID:8702519
↑ Rasko JE, Battini JL, Gottschalk RJ, Mazo I, Miller AD. The RD114/simian type D retrovirus receptor is a neutral amino acid transporter. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2129-34. PMID:10051606
↑ Tailor CS, Nouri A, Zhao Y, Takeuchi Y, Kabat D. A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses. J Virol. 1999 May;73(5):4470-4. PMID:10196349
↑ Tailor CS, Nouri A, Zhao Y, Takeuchi Y, Kabat D. A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses. J Virol. 1999 May;73(5):4470-4. PMID:10196349
↑ Tailor CS, Nouri A, Zhao Y, Takeuchi Y, Kabat D. A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses. J Virol. 1999 May;73(5):4470-4. PMID:10196349
↑ Canul-Tec JC, Assal R, Cirri E, Legrand P, Brier S, Chamot-Rooke J, Reyes N. Structure and allosteric inhibition of excitatory amino acid transporter 1. Nature. 2017 Apr 27;544(7651):446-451. doi: 10.1038/nature22064. Epub 2017 Apr, 19. PMID:28424515 doi:http://dx.doi.org/10.1038/nature22064

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5llu"

@@ Line 3: / Line 3: @@
 <StructureSection load='5llu' size='340' side='right'caption='[[5llu]], [[Resolution|resolution]] 3.32&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5llu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LLU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LLU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5llu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LLU 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=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]] 3.32&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5llm|5llm]]</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=NA:SODIUM+ION'>NA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC1A3, EAAT1, GLAST, GLAST1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5llu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5llu OCA], [https://pdbe.org/5llu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5llu RCSB], [https://www.ebi.ac.uk/pdbsum/5llu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5llu ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5llu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5llu OCA], [http://pdbe.org/5llu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5llu RCSB], [http://www.ebi.ac.uk/pdbsum/5llu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5llu ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/EAA1_HUMAN EAA1_HUMAN]] Alternating hemiplegia of childhood;Episodic ataxia type 6. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/EAA1_HUMAN EAA1_HUMAN] Alternating hemiplegia of childhood;Episodic ataxia type 6. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/EAA1_HUMAN EAA1_HUMAN]] Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
+[https://www.uniprot.org/uniprot/AAAT_HUMAN AAAT_HUMAN] Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids (PubMed:8702519). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development (PubMed:10708449, PubMed:23492904).<ref>PMID:10708449</ref> <ref>PMID:23492904</ref> <ref>PMID:8702519</ref>   (Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114.<ref>PMID:10051606</ref> <ref>PMID:10196349</ref>   (Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus.<ref>PMID:10196349</ref>   (Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.<ref>PMID:10196349</ref> [https://www.uniprot.org/uniprot/EAA1_HUMAN EAA1_HUMAN] Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Assal, R]]
+[[Category: Assal R]]
-[[Category: Canul-Tec, J]]
+[[Category: Canul-Tec J]]
-[[Category: Legrand, P]]
+[[Category: Legrand P]]
-[[Category: Reyes, N]]
+[[Category: Reyes N]]
-[[Category: Excitatory amino acid transporter 1]]
-[[Category: Human glutamate transporter]]
-[[Category: Slc1a3]]
-[[Category: Thermostabilized]]
-[[Category: Transport protein]]

5llu

From Proteopedia

Current revision

Structure of the thermostabilized EAAT1 cryst-II mutant in complex with L-ASP

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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