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| | ==Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in absence of substrate== | | ==Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in absence of substrate== |
| - | <StructureSection load='6rvy' size='340' side='right'caption='[[6rvy]], [[Resolution|resolution]] 4.13Å' scene=''> | + | <SX load='6rvy' size='340' side='right' viewer='molstar' caption='[[6rvy]], [[Resolution|resolution]] 4.13Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rvy]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RVY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RVY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rvy]] is a 3 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=6RVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RVY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6rvx|6rvx]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.13Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rvy OCA], [http://pdbe.org/6rvy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rvy RCSB], [http://www.ebi.ac.uk/pdbsum/6rvy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rvy 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=6rvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rvy OCA], [https://pdbe.org/6rvy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rvy RCSB], [https://www.ebi.ac.uk/pdbsum/6rvy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rvy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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/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> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The human Alanine Serine Cysteine Transporter 2 (ASCT2) is a neutral amino acid exchanger that belongs to the solute carrier family 1 (SLC1A). SLC1A structures have revealed an elevator-type mechanism, in which the substrate is translocated across the cell membrane by a large displacement of the transport domain, whereas a small movement of hairpin 2 (HP2) gates the extracellular access to the substrate-binding site. However, it has remained unclear how substrate binding and release is gated on the cytoplasmic side. Here, we present an inward-open structure of the human ASCT2, revealing a hitherto elusive SLC1A conformation. Strikingly, the same structural element (HP2) serves as a gate in the inward-facing as in the outward-facing state. The structures reveal that SLC1A transporters work as one-gate elevators. Unassigned densities near the gate and surrounding the scaffold domain, may represent potential allosteric binding sites, which could guide the design of lipidic-inhibitors for anticancer therapy. |
| | + | |
| | + | A one-gate elevator mechanism for the human neutral amino acid transporter ASCT2.,Garaeva AA, Guskov A, Slotboom DJ, Paulino C Nat Commun. 2019 Jul 31;10(1):3427. doi: 10.1038/s41467-019-11363-x. PMID:31366933<ref>PMID:31366933</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 6rvy" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garaeva, A A]] | + | [[Category: Garaeva AA]] |
| - | [[Category: Guskov, A]] | + | [[Category: Guskov A]] |
| - | [[Category: Paulino, C]] | + | [[Category: Paulino C]] |
| - | [[Category: Slotboom, D J]] | + | [[Category: Slotboom DJ]] |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
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]
Publication Abstract from PubMed
The human Alanine Serine Cysteine Transporter 2 (ASCT2) is a neutral amino acid exchanger that belongs to the solute carrier family 1 (SLC1A). SLC1A structures have revealed an elevator-type mechanism, in which the substrate is translocated across the cell membrane by a large displacement of the transport domain, whereas a small movement of hairpin 2 (HP2) gates the extracellular access to the substrate-binding site. However, it has remained unclear how substrate binding and release is gated on the cytoplasmic side. Here, we present an inward-open structure of the human ASCT2, revealing a hitherto elusive SLC1A conformation. Strikingly, the same structural element (HP2) serves as a gate in the inward-facing as in the outward-facing state. The structures reveal that SLC1A transporters work as one-gate elevators. Unassigned densities near the gate and surrounding the scaffold domain, may represent potential allosteric binding sites, which could guide the design of lipidic-inhibitors for anticancer therapy.
A one-gate elevator mechanism for the human neutral amino acid transporter ASCT2.,Garaeva AA, Guskov A, Slotboom DJ, Paulino C Nat Commun. 2019 Jul 31;10(1):3427. doi: 10.1038/s41467-019-11363-x. PMID:31366933[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
- ↑ Garaeva AA, Guskov A, Slotboom DJ, Paulino C. A one-gate elevator mechanism for the human neutral amino acid transporter ASCT2. Nat Commun. 2019 Jul 31;10(1):3427. doi: 10.1038/s41467-019-11363-x. PMID:31366933 doi:http://dx.doi.org/10.1038/s41467-019-11363-x
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