6zpd

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==gamma-tocopherol transfer protein==
==gamma-tocopherol transfer protein==
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<StructureSection load='6zpd' size='340' side='right'caption='[[6zpd]]' scene=''>
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<StructureSection load='6zpd' size='340' side='right'caption='[[6zpd]], [[Resolution|resolution]] 2.24&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=6ZPD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZPD FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6zpd]] 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=6ZPD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZPD 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=6zpd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zpd OCA], [http://pdbe.org/6zpd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zpd RCSB], [http://www.ebi.ac.uk/pdbsum/6zpd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zpd 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">X-ray diffraction, [[Resolution|Resolution]] 2.24&#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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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>
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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=6zpd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zpd OCA], [https://pdbe.org/6zpd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zpd RCSB], [https://www.ebi.ac.uk/pdbsum/6zpd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zpd ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/TTPA_HUMAN TTPA_HUMAN] Binds alpha-tocopherol and enhances its transfer between separate membranes.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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alpha-tocopherol transfer protein (TTP) was previously reported to self-aggregate into 24-meric spheres (alpha-TTP(S)) and to possess transcytotic potency across mono-layers of human umbilical vein endothelial cells (HUVECs). In this work, we describe the characterisation of a functional TTP variant with its vitamer selectivity shifted towards gamma-tocopherol. The shift was obtained by introducing an alanine to leucine substitution into the substrate-binding pocket at position 156 through site directed mutagenesis. We report here the X-ray crystal structure of the gamma-tocopherol specific particle (gamma-TTP(S)) at 2.24 A resolution. gamma-TTP(S) features full functionality compared to its alpha-tocopherol specific parent including self-aggregation potency and transcytotic activity in trans-well experiments using primary HUVEC cells. The impact of the A156L mutation on TTP function is quantified in vitro by measuring the affinity towards gamma-tocopherol through micro-differential scanning calorimetry and by determining its ligand-transfer activity. Finally, cell culture experiments using adherently grown HUVEC cells indicate that the protomers of gamma-TTP, in contrast to alpha-TTP, do not counteract cytokine-mediated inflammation at a transcriptional level. Our results suggest that the A156L substitution in TTP is fully functional and has the potential to pave the way for further experiments towards the understanding of alpha-tocopherol homeostasis in humans.
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Engineering of a functional gamma-tocopherol transfer protein.,Aeschimann W, Kammer S, Staats S, Schneider P, Schneider G, Rimbach G, Cascella M, Stocker A Redox Biol. 2021 Jan;38:101773. doi: 10.1016/j.redox.2020.101773. Epub 2020 Nov , 4. PMID:33197771<ref>PMID:33197771</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 6zpd" 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]]
[[Category: Aeschimann W]]
[[Category: Aeschimann W]]

Revision as of 11:55, 1 February 2024

gamma-tocopherol transfer protein

PDB ID 6zpd

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