8g0m
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of complex between TV6.6 and CD98hc ECD== | |
| + | <StructureSection load='8g0m' size='340' side='right'caption='[[8g0m]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8g0m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G0M FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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=8g0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g0m OCA], [https://pdbe.org/8g0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g0m RCSB], [https://www.ebi.ac.uk/pdbsum/8g0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g0m ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV(CD98hc)). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV(CD98hc)) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATV(CD98hc) demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATV(CD98hc) that impact FcgammaR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TV(CD98hc) as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms. | ||
| - | + | CD98hc is a target for brain delivery of biotherapeutics.,Chew KS, Wells RC, Moshkforoush A, Chan D, Lechtenberg KJ, Tran HL, Chow J, Kim DJ, Robles-Colmenares Y, Srivastava DB, Tong RK, Tong M, Xa K, Yang A, Zhou Y, Akkapeddi P, Annamalai L, Bajc K, Blanchette M, Cherf GM, Earr TK, Gill A, Huynh D, Joy D, Knight KN, Lac D, Leung AW, Lexa KW, Liau NPD, Becerra I, Malfavon M, McInnes J, Nguyen HN, Lozano EI, Pizzo ME, Roche E, Sacayon P, Calvert MEK, Daneman R, Dennis MS, Duque J, Gadkar K, Lewcock JW, Mahon CS, Meisner R, Solanoy H, Thorne RG, Watts RJ, Zuchero YJY, Kariolis MS Nat Commun. 2023 Aug 19;14(1):5053. doi: 10.1038/s41467-023-40681-4. PMID:37598178<ref>PMID:37598178</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8g0m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Kariolis MS]] | ||
| + | [[Category: Lexa K]] | ||
| + | [[Category: Liau NPD]] | ||
| + | [[Category: Srivastava D]] | ||
| + | [[Category: Tran H]] | ||
| + | [[Category: Wells RC]] | ||
Current revision
Structure of complex between TV6.6 and CD98hc ECD
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