6jmq

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'''Unreleased structure'''
 
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The entry 6jmq is ON HOLD until Paper Publication
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==LAT1-CD98hc complex bound to MEM-108 Fab==
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<SX load='6jmq' size='340' side='right' viewer='molstar' caption='[[6jmq]], [[Resolution|resolution]] 3.31&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6jmq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JMQ FirstGlance]. <br>
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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]] 3.31&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6jmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jmq OCA], [https://pdbe.org/6jmq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jmq RCSB], [https://www.ebi.ac.uk/pdbsum/6jmq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jmq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The L-type amino acid transporter 1 (LAT1 or SLC7A5) transports large neutral amino acids across the membrane and is crucial for brain drug delivery and tumor growth. LAT1 forms a disulfide-linked heterodimer with CD98 heavy chain (CD98hc, 4F2hc or SLC3A2), but the mechanism of assembly and amino acid transport are poorly understood. Here we report the cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3-A resolution. LAT1 features a canonical Leu T-fold and exhibits an unusual loop structure on transmembrane helix 6, creating an extended cavity that might accommodate bulky amino acids and drugs. CD98hc engages with LAT1 through the extracellular, transmembrane and putative cholesterol-mediated interactions. We also show that two anti-CD98 antibodies recognize distinct, multiple epitopes on CD98hc but not its glycans, explaining their robust reactivities. These results reveal the principles of glycoprotein-solute carrier assembly and provide templates for improving preclinical drugs and antibodies targeting LAT1 or CD98hc.
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Authors:
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Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc.,Lee Y, Wiriyasermkul P, Jin C, Quan L, Ohgaki R, Okuda S, Kusakizako T, Nishizawa T, Oda K, Ishitani R, Yokoyama T, Nakane T, Shirouzu M, Endou H, Nagamori S, Kanai Y, Nureki O Nat Struct Mol Biol. 2019 Jun;26(6):510-517. doi: 10.1038/s41594-019-0237-7. Epub, 2019 Jun 3. PMID:31160781<ref>PMID:31160781</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 6jmq" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[3D structures of non-human antibody|3D structures of non-human antibody]]
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== References ==
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<references/>
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__TOC__
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</SX>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Ishitani R]]
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[[Category: Kusakizako T]]
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[[Category: Lee Y]]
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[[Category: Nakane T]]
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[[Category: Nishizawa T]]
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[[Category: Nureki O]]
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[[Category: Oda K]]

Current revision

LAT1-CD98hc complex bound to MEM-108 Fab

6jmq, resolution 3.31Å

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