6mpb

From Proteopedia

(Difference between revisions)

Revision as of 08:52, 27 November 2019

Cryo-EM structure of the human neutral amino acid transporter ASCT2

Structural highlights

6mpb 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.
Ligands:	,
Gene:	SLC1A5, ASCT2, M7V1, RDR, RDRC (HUMAN)
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

Alanine-serine-cysteine transporter 2 (ASCT2, SLC1A5) is the primary transporter of glutamine in cancer cells and regulates the mTORC1 signaling pathway. The SLC1A5 function involves finely tuned orchestration of two domain movements that include the substrate-binding transport domain and the scaffold domain. Here, we present cryo-EM structures of human SLC1A5 and its complex with the substrate, L-glutamine in an outward-facing conformation. These structures reveal insights into the conformation of the critical ECL2a loop which connects the two domains, thus allowing rigid body movement of the transport domain throughout the transport cycle. Furthermore, the structures provide new insights into substrate recognition, which involves conformational changes in the HP2 loop. A putative cholesterol binding site was observed near the domain interface in the outward-facing state. Comparison with the previously determined inward-facing structure of SCL1A5 provides a basis for a more integrated understanding of substrate recognition and transport mechanism in the SLC1 family.

Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.,Yu X, Plotnikova O, Bonin PD, Subashi TA, McLellan TJ, Dumlao D, Che Y, Dong YY, Carpenter EP, West GM, Qiu X, Culp JS, Han S Elife. 2019 Oct 3;8. pii: 48120. doi: 10.7554/eLife.48120. PMID:31580259^[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
↑ Yu X, Plotnikova O, Bonin PD, Subashi TA, McLellan TJ, Dumlao D, Che Y, Dong YY, Carpenter EP, West GM, Qiu X, Culp JS, Han S. Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation. Elife. 2019 Oct 3;8. pii: 48120. doi: 10.7554/eLife.48120. PMID:31580259 doi:http://dx.doi.org/10.7554/eLife.48120

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/6mpb"

@@ Line 3: / Line 3: @@
 <StructureSection load='6mpb' size='340' side='right'caption='[[6mpb]], [[Resolution|resolution]] 3.84&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mpb]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MPB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MPB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mpb]] 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=6MPB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MPB FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6mpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mpb OCA], [http://pdbe.org/6mpb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mpb RCSB], [http://www.ebi.ac.uk/pdbsum/6mpb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mpb ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Han, S]]

6mpb

From Proteopedia

Revision as of 08:52, 27 November 2019

Cryo-EM structure of the human neutral amino acid transporter ASCT2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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