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| | ==Structure of Human Ferritin L Chain== | | ==Structure of Human Ferritin L Chain== |
| - | <StructureSection load='2fg4' size='340' side='right' caption='[[2fg4]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='2fg4' size='340' side='right'caption='[[2fg4]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fg4]] is a 1 chain structure with 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=2FG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FG4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fg4]] 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=2FG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FG4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ffx|2ffx]], [[2fg8|2fg8]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FTL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2fg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fg4 OCA], [https://pdbe.org/2fg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fg4 RCSB], [https://www.ebi.ac.uk/pdbsum/2fg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fg4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fg4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2fg4 RCSB], [http://www.ebi.ac.uk/pdbsum/2fg4 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/FRIL_HUMAN FRIL_HUMAN]] Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:[http://omim.org/entry/600886 600886]]. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene.<ref>PMID:20159981</ref> Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:[http://omim.org/entry/606159 606159]]; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.<ref>PMID:20159981</ref> <ref>PMID:16116125</ref> | + | [https://www.uniprot.org/uniprot/FRIL_HUMAN FRIL_HUMAN] Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:[https://omim.org/entry/600886 600886]. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene.<ref>PMID:20159981</ref> Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:[https://omim.org/entry/606159 606159]; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.<ref>PMID:20159981</ref> <ref>PMID:16116125</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FRIL_HUMAN FRIL_HUMAN]] Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).<ref>PMID:19923220</ref> <ref>PMID:20159981</ref> | + | [https://www.uniprot.org/uniprot/FRIL_HUMAN FRIL_HUMAN] Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).<ref>PMID:19923220</ref> <ref>PMID:20159981</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fg/2fg4_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fg/2fg4_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=2fg4 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2fg4" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ferritin|Ferritin]] | + | *[[Ferritin 3D structures|Ferritin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Carter, D C]] | + | [[Category: Large Structures]] |
| - | [[Category: Ellenburg, M]] | + | [[Category: Carter DC]] |
| - | [[Category: Ho, J X]] | + | [[Category: Ellenburg M]] |
| - | [[Category: Li, C]] | + | [[Category: Ho JX]] |
| - | [[Category: Ruble, J]] | + | [[Category: Li C]] |
| - | [[Category: Wang, Z]] | + | [[Category: Ruble J]] |
| - | [[Category: Human light chain ferritin]]
| + | [[Category: Wang Z]] |
| - | [[Category: Metal binding protein]]
| + | |
| Structural highlights
Disease
FRIL_HUMAN Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:600886. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene.[1] Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:606159; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.[2] [3]
Function
FRIL_HUMAN Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).[4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ferritin is the major iron-storage protein present in all cells. It generally contains 24 subunits, with different ratios of heavy chain (H) to light chain (L), in the shape of a hollow sphere hosting up to 4500 ferric Fe atoms inside. H-rich ferritins catalyse the oxidation of iron(II), while L-rich ferritins promote the nucleation and storage of iron(III). Several X-ray structures have been determined, including those of L-chain ferritins from horse spleen (HoSF), recombinant L-chain ferritins from horse (HoLF), mouse (MoLF) and bullfrog (BfLF) as well as recombinant human H-chain ferritin (HuHF). Here, structures have been determined of two crystal forms of recombinant human L-chain ferritin (HuLF) obtained from native and perdeuterated proteins. The structures show a cluster of acidic residues at the ferrihydrite nucleation site and at the iron channel along the threefold axis. An ordered Cd2+ structure is observed within the iron channel, offering further insight into the route and mechanism of iron transport into the capsid. The loop between helices D and E, which is disordered in many other L-chain structures, is clearly visible in these two structures. The crystals generated from perdeuterated HuLF will be used for neutron diffraction studies.
Structure of human ferritin L chain.,Wang Z, Li C, Ellenburg M, Soistman E, Ruble J, Wright B, Ho JX, Carter DC Acta Crystallogr D Biol Crystallogr. 2006 Jul;62(Pt 7):800-6. Epub 2006, Jun 20. PMID:16790936[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P. Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981 doi:10.1074/jbc.M109.096404
- ↑ Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P. Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981 doi:10.1074/jbc.M109.096404
- ↑ Maciel P, Cruz VT, Constante M, Iniesta I, Costa MC, Gallati S, Sousa N, Sequeiros J, Coutinho P, Santos MM. Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement. Neurology. 2005 Aug 23;65(4):603-5. PMID:16116125 doi:10.1212/01.wnl.0000178224.81169.c2
- ↑ Baraibar MA, Muhoberac BB, Garringer HJ, Hurley TD, Vidal R. Unraveling of the E-helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration. J Biol Chem. 2010 Jan 15;285(3):1950-6. Epub 2009 Nov 18. PMID:19923220 doi:10.1074/jbc.M109.042986
- ↑ Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P. Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation. J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981 doi:10.1074/jbc.M109.096404
- ↑ Wang Z, Li C, Ellenburg M, Soistman E, Ruble J, Wright B, Ho JX, Carter DC. Structure of human ferritin L chain. Acta Crystallogr D Biol Crystallogr. 2006 Jul;62(Pt 7):800-6. Epub 2006, Jun 20. PMID:16790936 doi:10.1107/S0907444906018294
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