|
|
| (14 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1oiz.jpg|left|200px]] | |
| | | | |
| - | {{Structure
| + | ==The Molecular Basis of Vitamin E Retention: Structure of Human Alpha-Tocopherol Transfer Protein== |
| - | |PDB= 1oiz |SIZE=350|CAPTION= <scene name='initialview01'>1oiz</scene>, resolution 1.88Å
| + | <StructureSection load='1oiz' size='340' side='right'caption='[[1oiz]], [[Resolution|resolution]] 1.88Å' scene=''> |
| - | |SITE= <scene name='pdbsite=AC1:Trt+Binding+Site+For+Chain+A'>AC1</scene>
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=TRT:FRAGMENT OF TRITON X-100'>TRT</scene>
| + | <table><tr><td colspan='2'>[[1oiz]] is a 2 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=1OIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OIZ FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</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=1oiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oiz OCA], [https://pdbe.org/1oiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oiz RCSB], [https://www.ebi.ac.uk/pdbsum/1oiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oiz ProSAT]</span></td></tr> |
| - | | + | </table> |
| - | '''THE MOLECULAR BASIS OF VITAMIN E RETENTION: STRUCTURE OF HUMAN ALPHA-TOCOPHEROL TRANSFER PROTEIN'''
| + | == 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 == |
| - | ==Overview==
| + | [https://www.uniprot.org/uniprot/TTPA_HUMAN TTPA_HUMAN] Binds alpha-tocopherol and enhances its transfer between separate membranes. |
| - | Alpha-tocopherol transfer protein (alpha-TTP) is a liver protein responsible for the selective retention of alpha-tocopherol from dietary vitamin E, which is a mixture of alpha, beta, gamma, and delta-tocopherols and the corresponding tocotrienols. The alpha-TTP-mediated transfer of alpha-tocopherol into nascent VLDL is the major determinant of plasma alpha-tocopherol levels in humans. Mutations in the alpha-TTP gene have been detected in patients suffering from low plasma alpha-tocopherol and ataxia with isolated vitamin E deficiency (AVED). The crystal structure of alpha-TTP reveals two conformations. In its closed tocopherol-charged form, a mobile helical surface segment seals the hydrophobic binding pocket. In the presence of detergents, an open conformation is observed, which probably represents the membrane-bound form. The selectivity of alpha-TTP for RRR-alpha-tocopherol is explained from the van der Waals contacts occurring in the lipid-binding pocket. Mapping the known mutations leading to AVED onto the crystal structure shows that no mutations occur directly in the binding pocket.
| + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | ==Disease== | + | Check<jmol> |
| - | Known diseases associated with this structure: Ataxia with isolated vitamin E deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600415 600415]], Ceroid-lipofuscinosis, neuronal 2, classic late infantile OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607998 607998]]
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oi/1oiz_consurf.spt"</scriptWhenChecked> |
| - | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | 1OIZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OIZ OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==Reference== | + | </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=1oiz ConSurf]. |
| - | The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein., Meier R, Tomizaki T, Schulze-Briese C, Baumann U, Stocker A, J Mol Biol. 2003 Aug 15;331(3):725-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12899840 12899840]
| + | <div style="clear:both"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Baumann, U.]] | + | [[Category: Baumann U]] |
| - | [[Category: Meier, R.]] | + | [[Category: Meier R]] |
| - | [[Category: Schulze-Briese, C.]] | + | [[Category: Schulze-Briese C]] |
| - | [[Category: Stocker, A.]] | + | [[Category: Stocker A]] |
| - | [[Category: Tomizaki, T.]] | + | [[Category: Tomizaki T]] |
| - | [[Category: TRT]]
| + | |
| - | [[Category: ataxia]]
| + | |
| - | [[Category: aved]]
| + | |
| - | [[Category: tocopherol]]
| + | |
| - | [[Category: transfer protein]]
| + | |
| - | [[Category: transport]]
| + | |
| - | [[Category: vitamin e]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:11:34 2008''
| + | |
| Structural highlights
Disease
TTPA_HUMAN Defects in TTPA are the cause of ataxia with isolated vitamin E deficiency (AVED) [MIM: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.[1] [2] [3] [4] [5] [6]
Function
TTPA_HUMAN Binds alpha-tocopherol and enhances its transfer between separate membranes.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Hentati A, Deng HX, Hung WY, Nayer M, Ahmed MS, He X, Tim R, Stumpf DA, Siddique T, Ahmed. Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency. Ann Neurol. 1996 Mar;39(3):295-300. PMID:8602747 doi:http://dx.doi.org/10.1002/ana.410390305
- ↑ Cavalier L, Ouahchi K, Kayden HJ, Di Donato S, Reutenauer L, Mandel JL, Koenig M. Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet. 1998 Feb;62(2):301-10. PMID:9463307 doi:S0002-9297(07)63495-8
- ↑ Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Arai H, Inoue K, Mandel JL, Koenig M. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein. Nat Genet. 1995 Feb;9(2):141-5. PMID:7719340 doi:http://dx.doi.org/10.1038/ng0295-141
- ↑ Gotoda T, Arita M, Arai H, Inoue K, Yokota T, Fukuo Y, Yazaki Y, Yamada N. Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein. N Engl J Med. 1995 Nov 16;333(20):1313-8. PMID:7566022
- ↑ Morley S, Panagabko C, Shineman D, Mani B, Stocker A, Atkinson J, Manor D. Molecular determinants of heritable vitamin E deficiency. Biochemistry. 2004 Apr 13;43(14):4143-9. PMID:15065857 doi:10.1021/bi0363073
- ↑ Mariotti C, Gellera C, Rimoldi M, Mineri R, Uziel G, Zorzi G, Pareyson D, Piccolo G, Gambi D, Piacentini S, Squitieri F, Capra R, Castellotti B, Di Donato S. Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families. Neurol Sci. 2004 Jul;25(3):130-7. PMID:15300460 doi:10.1007/s10072-004-0246-z
|
