View source for 5mue


==Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier==
<StructureSection load='5mue' size='340' side='right'caption='[[5mue]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mue]] is a 1 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=5MUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MUE 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]] 2.397&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ETA:ETHANOLAMINE'>ETA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VIV:(2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL'>VIV</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=5mue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mue OCA], [https://pdbe.org/5mue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mue RCSB], [https://www.ebi.ac.uk/pdbsum/5mue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mue ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TTPA_HUMAN TTPA_HUMAN] Defects in TTPA are the cause of ataxia with isolated vitamin E deficiency (AVED) [MIM:[https://omim.org/entry/277460 277460]. AVED is an autosomal recessive disease characterized by spinocerebellar degeneration. It causes ataxia and peripheral neuropathy that resembles Friedreich ataxia. AVED patients have markedly reduced plasma levels of vitamin E.<ref>PMID:8602747</ref> <ref>PMID:9463307</ref> <ref>PMID:7719340</ref> <ref>PMID:7566022</ref> <ref>PMID:15065857</ref> <ref>PMID:15300460</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TTPA_HUMAN TTPA_HUMAN] Binds alpha-tocopherol and enhances its transfer between separate membranes.
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== Publication Abstract from PubMed ==
Vitamin E is one of the most important natural antioxidants, protecting polyunsaturated fatty acids in the membranes of cells. Among different chemical isoforms assimilated from dietary regimes, RRR-alpha-tocopherol is the only one retained in higher animals. This is possible thanks to alpha-Tocopherol Transfer Protein (alpha-TTP), which extracts alpha-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, alpha-TTP acquires tendency to aggregation into thermodynamically stable high molecular weight oligomers. Determination of the structure of such aggregates by X-ray crystallography revealed a spheroidal particle formed by 24 protein monomers. Oligomerization is triggered by refolding of the N-terminus. Experiments with cultured cell monolayers demonstrate that the same oligomers are efficiently transported through an endothelial barrier (HUVEC) and not through an epithelial one (Caco-2). Discovery of a human endogenous transport protein with intrinsic capability of crossing endothelial tissues opens to new ways of drug delivery into the brain or other tissues protected by endothelial barriers.

Self-assembled alpha-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier.,Aeschimann W, Staats S, Kammer S, Olieric N, Jeckelmann JM, Fotiadis D, Netscher T, Rimbach G, Cascella M, Stocker A Sci Rep. 2017 Jul 10;7(1):4970. doi: 10.1038/s41598-017-05148-9. PMID:28694484<ref>PMID:28694484</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aeschimann W]]
[[Category: Stocker A]]