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1r5l

From Proteopedia

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(New page: 200px<br /> <applet load="1r5l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r5l, resolution 1.50&Aring;" /> '''Crystal Structure o...)
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[[Image:1r5l.gif|left|200px]]<br />
 
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<applet load="1r5l" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1r5l, resolution 1.50&Aring;" />
 
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'''Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand'''<br />
 
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==Overview==
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==Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand==
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Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central, role in vitamin E homeostasis, preventing degradation of alpha-T by, routing this lipophilic molecule for secretion by hepatocytes. Mutations, in the gene encoding ATTP have been shown to cause a severe deficiency in, alpha-T, which results in a progressive neurodegenerative spinocerebellar, ataxia, known as ataxia with vitamin E deficiency (AVED). We have, determined the high-resolution crystal structure of human ATTP with, (2R,4'R,8'R)-alpha-T in the binding pocket. Surprisingly, the ligand is, sequestered deep in the hydrophobic core of the protein, implicating a, large structural rearrangement for the entry and release of alpha-T. A, comparison to the structure of a related protein, Sec14p, crystallized, without a bona fide ligand, shows a possibly relevant open conformation, for this family of proteins. Furthermore, of the known mutations that, cause AVED, one mutation, L183P, is located directly in the binding, pocket. Finally, three mutations associated with AVED involve arginine, residues that are grouped together on the surface of ATTP. We propose that, this positively charged surface may serve to orient an interacting, protein, which might function to regulate the release of alpha-T through, an induced change in conformation of ATTP.
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<StructureSection load='1r5l' size='340' side='right'caption='[[1r5l]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1r5l]] 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=1R5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R5L FirstGlance]. <br>
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Known disease associated with this structure: Ataxia with isolated vitamin E deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600415 600415]]
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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]] 1.5&#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=MSE:SELENOMETHIONINE'>MSE</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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==About this Structure==
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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=1r5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r5l OCA], [https://pdbe.org/1r5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r5l RCSB], [https://www.ebi.ac.uk/pdbsum/1r5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r5l ProSAT]</span></td></tr>
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1R5L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with VIV as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R5L OCA].
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</table>
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== Disease ==
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==Reference==
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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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Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency., Min KC, Kovall RA, Hendrickson WA, Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8. Epub 2003 Dec 1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14657365 14657365]
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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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r5/1r5l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1r5l ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Hendrickson, W.A.]]
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[[Category: Hendrickson WA]]
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[[Category: Kovall, R.A.]]
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[[Category: Kovall RA]]
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[[Category: Min, K.C.]]
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[[Category: Min KC]]
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[[Category: VIV]]
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[[Category: ataxia with vitamin e deficiency]]
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[[Category: attp]]
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[[Category: tocopherol]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:00:31 2007''
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Current revision

Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand

PDB ID 1r5l

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