View source for 8qrw


==ASCT2 protomer in lipid nanodiscs under low Na+ concentration in the intermediate outward-facing state (iOFS-up)==
<StructureSection load='8qrw' size='340' side='right'caption='[[8qrw]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qrw]] 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=8QRW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QRW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</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=8qrw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qrw OCA], [https://pdbe.org/8qrw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qrw RCSB], [https://www.ebi.ac.uk/pdbsum/8qrw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qrw ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== Publication Abstract from PubMed ==
ASCT2 is an obligate exchanger of neutral amino acids, contributing to cellular amino acid homeostasis. ASCT2 belongs to the same family (SLC1) as Excitatory Amino Acid Transporters (EAATs) that concentrate glutamate in the cytosol. The mechanism that makes ASCT2 an exchanger rather than a concentrator remains enigmatic. Here, we employ cryo-electron microscopy and molecular dynamics simulations to elucidate the structural basis of the exchange mechanism of ASCT2. We establish that ASCT2 binds three Na(+) ions per transported substrate and visits a state that likely acts as checkpoint in preventing Na(+) ion leakage, both features shared with EAATs. However, in contrast to EAATs, ASCT2 retains one Na(+) ion even under Na(+)-depleted conditions. We demonstrate that ASCT2 cannot undergo the structural transition in TM7 that is essential for the concentrative transport cycle of EAATs. This structural rigidity and the high-affinity Na(+) binding site effectively confine ASCT2 to an exchange mode.

Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.,Borowska AM, Chiariello MG, Garaeva AA, Rheinberger J, Marrink SJ, Paulino C, Slotboom DJ Nat Commun. 2024 Aug 3;15(1):6570. doi: 10.1038/s41467-024-50888-8. PMID:39095408<ref>PMID:39095408</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Borowska A]]
[[Category: Paulino C]]
[[Category: Rheinberger J]]
[[Category: Slotboom DJ]]