7ccs

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Current revision (06:10, 21 November 2024) (edit) (undo)
 
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==Consensus mutated xCT-CD98hc complex==
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<StructureSection load='7ccs' size='340' side='right'caption='[[7ccs]]' scene=''>
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<StructureSection load='7ccs' size='340' side='right'caption='[[7ccs]], [[Resolution|resolution]] 6.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7ccs]] is a 2 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=7CCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CCS FirstGlance]. <br>
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</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=7ccs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ccs OCA], [http://pdbe.org/7ccs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7ccs RCSB], [http://www.ebi.ac.uk/pdbsum/7ccs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7ccs ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.2&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ccs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ccs OCA], [https://pdbe.org/7ccs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ccs RCSB], [https://www.ebi.ac.uk/pdbsum/7ccs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ccs ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/4F2_HUMAN 4F2_HUMAN] Required for the function of light chain amino-acid transporters. Involved in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. Involved in guiding and targeting of LAT1 and LAT2 to the plasma membrane. When associated with SLC7A6 or SLC7A7 acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Required for normal and neoplastic cell growth. When associated with SLC7A5/LAT1, is also involved in the transport of L-DOPA across the blood-brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. When associated with SLC7A5 or SLC7A8, involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Together with ICAM1, regulates the transport activity LAT2 in polarized intestinal cells, by generating and delivering intracellular signals. When associated with SLC7A5, plays an important role in transporting L-leucine from the circulating blood to the retina across the inner blood-retinal barrier.<ref>PMID:11557028</ref> <ref>PMID:9829974</ref> <ref>PMID:9751058</ref> <ref>PMID:9878049</ref> <ref>PMID:10903140</ref> <ref>PMID:11311135</ref> <ref>PMID:11389679</ref> <ref>PMID:11564694</ref> <ref>PMID:11742812</ref> <ref>PMID:12117417</ref> <ref>PMID:12225859</ref> <ref>PMID:14603368</ref> <ref>PMID:12716892</ref> <ref>PMID:15980244</ref> <ref>PMID:15769744</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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System x(c) (-) is an amino acid antiporter that imports L-cystine into cells and exports intracellular L-glutamate, at a 1:1 ratio. As L-cystine is an essential precursor for glutathione synthesis, system x(c) (-) supports tumor cell growth through glutathione-based oxidative stress resistance and is considered as a potential therapeutic target for cancer treatment. System x(c) (-) consists of two subunits, the light chain subunit SLC7A11 (xCT) and the heavy chain subunit SLC3A2 (also known as CD98hc or 4F2hc), which are linked by a conserved disulfide bridge. Although the recent structures of another SLC7 member, L-type amino acid transporter 1 (LAT1) in complex with CD98hc, have provided the structural basis toward understanding the amino acid transport mechanism, the detailed molecular mechanism of xCT remains unknown. To revealthe molecular mechanism, we performed single-particle analyses of the xCT-CD98hc complex. As wild-type xCT-CD98hc displayed poor stability and could not be purified to homogeneity, we applied a consensus mutagenesis approach to xCT. The consensus mutated construct exhibited increased stability as compared to the wild-type, and enabled the cryoelectron microscopy (cryo-EM) map to be obtained at 6.2 A resolution by single-particle analysis. The cryo-EM map revealed sufficient electron density to assign secondary structures. In the xCT structure, the hash and arm domains are well resolved, whereas the bundle domain shows some flexibility. CD98hc is positioned next to the xCT transmembrane domain. This study provides the structural basis of xCT, and our consensus-based strategy could represent a good choice toward solving unstable protein structures.
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Consensus mutagenesis approach improves the thermal stability of system x(c) (-) transporter, xCT, and enables cryo-EM analyses.,Oda K, Lee Y, Wiriyasermkul P, Tanaka Y, Takemoto M, Yamashita K, Nagamori S, Nishizawa T, Nureki O Protein Sci. 2020 Dec;29(12):2398-2407. doi: 10.1002/pro.3966. Epub 2020 Nov 11. PMID:33016372<ref>PMID:33016372</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7ccs" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Lee Y]]
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[[Category: Nishizawa T]]
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[[Category: Nureki O]]
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[[Category: Oda K]]
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[[Category: Takemoto M]]
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[[Category: Yamashita K]]

Current revision

Consensus mutated xCT-CD98hc complex

PDB ID 7ccs

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