6irt
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==human LAT1-4F2hc complex bound with BCH== | |
| + | <StructureSection load='6irt' size='340' side='right'caption='[[6irt]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6irt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IRT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IRT FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PH:1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE'>3PH</scene>, <scene name='pdbligand=AUU:(1S,2S,4R)-2-aminobicyclo[2.2.1]heptane-2-carboxylic+acid'>AUU</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6irt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6irt OCA], [http://pdbe.org/6irt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6irt RCSB], [http://www.ebi.ac.uk/pdbsum/6irt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6irt ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/LAT1_HUMAN LAT1_HUMAN]] Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular amino acid uptake. Acts as an amino acid exchanger. 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. Plays a role in neuronal cell proliferation (neurogenesis) in brain. 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. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. May play an important role in high-grade gliomas. Mediates blood-to-retina L-leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts. When associated with LAPTM4B, recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567).<ref>PMID:10049700</ref> <ref>PMID:10391915</ref> <ref>PMID:10574970</ref> <ref>PMID:11311135</ref> <ref>PMID:11389679</ref> <ref>PMID:11557028</ref> <ref>PMID:11564694</ref> <ref>PMID:11742812</ref> <ref>PMID:12117417</ref> <ref>PMID:12225859</ref> <ref>PMID:15769744</ref> <ref>PMID:16496379</ref> <ref>PMID:18262359</ref> <ref>PMID:25998567</ref> <ref>PMID:9751058</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner(1-3). LAT1, an antiporter of the amino acid-polyamine-organocation superfamily, also catalyses the permeation of thyroid hormones, pharmaceutical drugs, and hormone precursors such as L-3,4-dihydroxyphenylalanine across membranes(2-6). Overexpression of LAT1 has been observed in a wide range of tumour cells, and it is thus a potential target for anti-cancer drugs(7-11). LAT1 forms a heteromeric amino acid transporter complex with 4F2 cell-surface antigen heavy chain (4F2hc; also known as SLC3A2)-a type II membrane glycoprotein that is essential for the stability of LAT1 and for its localization to the plasma membrane(8,9). Despite extensive cell-based characterization of the LAT1-4F2hc complex and structural determination of its homologues in bacteria, the interactions between LAT1 and 4F2hc and the working mechanism of the complex remain largely unknown(12-19). Here we report the cryo-electron microscopy structures of human LAT1-4F2hc alone and in complex with the inhibitor 2-amino-2-norbornanecarboxylic acid at resolutions of 3.3 A and 3.5 A, respectively. LAT1 exhibits an inward open conformation. Besides a disulfide bond association, LAT1 also interacts extensively with 4F2hc on the extracellular side, within the membrane, and on the intracellular side. Biochemical analysis reveals that 4F2hc is essential for the transport activity of the complex. Together, our characterizations shed light on the architecture of the LAT1-4F2hc complex, and provide insights into its function and the mechanisms through which it might be associated with disease. | ||
| - | + | Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.,Yan R, Zhao X, Lei J, Zhou Q Nature. 2019 Mar 13. pii: 10.1038/s41586-019-1011-z. doi:, 10.1038/s41586-019-1011-z. PMID:30867591<ref>PMID:30867591</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6irt" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lei, J L]] | ||
| + | [[Category: Yan, R H]] | ||
| + | [[Category: Zhao, X]] | ||
| + | [[Category: Zhou, Q]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Transporter]] | ||
Revision as of 06:41, 27 March 2019
human LAT1-4F2hc complex bound with BCH
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