7awm

From Proteopedia

(Difference between revisions)

Current revision

Structure of the thermostabilized EAAT1 cryst mutant in complex with L-ASP, three sodium ions and the allosteric inhibitor UCPH101

Structural highlights

7awm 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 3.25Å
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

Excitatory amino acid transporters (EAATs) maintain glutamate gradients in the brain essential for neurotransmission and to prevent neuronal death. They use ionic gradients as energy source and co-transport transmitter into the cytoplasm with Na(+) and H(+) , while counter-transporting K(+) to re-initiate the transport cycle. However, the molecular mechanisms underlying ion-coupled transport remain incompletely understood. Here, we present 3D X-ray crystallographic and cryo-EM structures, as well as thermodynamic analysis of human EAAT1 in different ion bound conformations, including elusive counter-transport ion bound states. Binding energies of Na(+) and H(+) , and unexpectedly Ca(2+) , are coupled to neurotransmitter binding. Ca(2+) competes for a conserved Na(+) site, suggesting a regulatory role for Ca(2+) in glutamate transport at the synapse, while H(+) binds to a conserved glutamate residue stabilizing substrate occlusion. The counter-transported ion binding site overlaps with that of glutamate, revealing the K(+) -based mechanism to exclude the transmitter during the transport cycle and to prevent its neurotoxic release on the extracellular side.

The ion-coupling mechanism of human excitatory amino acid transporters.,Canul-Tec JC, Kumar A, Dhenin J, Assal R, Legrand P, Rey M, Chamot-Rooke J, Reyes N EMBO J. 2021 Nov 8:e108341. doi: 10.15252/embj.2021108341. PMID:34747040^[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, Kumar A, Dhenin J, Assal R, Legrand P, Rey M, Chamot-Rooke J, Reyes N. The ion-coupling mechanism of human excitatory amino acid transporters. EMBO J. 2021 Nov 8:e108341. doi: 10.15252/embj.2021108341. PMID:34747040 doi:http://dx.doi.org/10.15252/embj.2021108341

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/7awm"

Categories: Homo sapiens | Large Structures | Canul-Tec JC | Legrand P | Reyes N

@@ Line 3: / Line 3: @@
 <StructureSection load='7awm' size='340' side='right'caption='[[7awm]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7awm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7awm]] 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=7AWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Z6:2-AMINO-5,6,7,8-TETRAHYDRO-4-(4-METHOXYPHENYL)-7-(NAPHTHALEN-1-YL)-5-OXO-4H-CHROMENE-3-CARBONITRILE'>6Z6</scene>, <scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=BA:BARIUM+ION'>BA</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]] 3.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6Z6:2-AMINO-5,6,7,8-TETRAHYDRO-4-(4-METHOXYPHENYL)-7-(NAPHTHALEN-1-YL)-5-OXO-4H-CHROMENE-3-CARBONITRILE'>6Z6</scene>, <scene name='pdbligand=ASP:ASPARTIC+ACID'>ASP</scene>, <scene name='pdbligand=BA:BARIUM+ION'>BA</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=7awm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awm OCA], [https://pdbe.org/7awm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awm RCSB], [https://www.ebi.ac.uk/pdbsum/7awm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awm ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[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.
+[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 ==
-[[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.
+[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 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Canul-Tec, J C]]
+[[Category: Canul-Tec JC]]
-[[Category: Legrand, P]]
+[[Category: Legrand P]]
-[[Category: Reyes, N]]
+[[Category: Reyes N]]
-[[Category: Allosteric inhibitor ucph101]]
-[[Category: Excitatory amino acid transporter 1]]
-[[Category: Human glutamate transporter]]
-[[Category: Membrane protein]]
-[[Category: Slc1a3]]

7awm

From Proteopedia

Current revision

Structure of the thermostabilized EAAT1 cryst mutant in complex with L-ASP, three sodium ions and the allosteric inhibitor UCPH101

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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