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6rvy

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Revision as of 05:52, 11 April 2020

Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in absence of substrate

6rvy, resolution 4.13Å

Structural highlights

6rvy is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	6rvx
Gene:	SLC1A5, ASCT2, M7V1, RDR, RDRC (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6rvy"

@@ Line 3: / Line 3: @@
 <SX load='6rvy' size='340' side='right' viewer='molstar' caption='[[6rvy]], [[Resolution|resolution]] 4.13&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rvy]] is a 3 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=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 [http://en.wikipedia.org/wiki/Human Human]. 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://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>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC1A5, ASCT2, M7V1, RDR, RDRC ([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'>[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'>[http://proteopedia.org/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>
 </table>
 == Function ==

6rvy

From Proteopedia

Revision as of 05:52, 11 April 2020

Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in absence of substrate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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