3kxu

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{{Seed}}
 
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[[Image:3kxu.png|left|200px]]
 
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==Crystal structure of human ferritin FTL498InsTC pathogenic mutant==
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The line below this paragraph, containing "STRUCTURE_3kxu", creates the "Structure Box" on the page.
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<StructureSection load='3kxu' size='340' side='right'caption='[[3kxu]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3kxu]] 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=3KXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KXU FirstGlance]. <br>
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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]] 1.85&#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=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_3kxu| PDB=3kxu | SCENE= }}
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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=3kxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kxu OCA], [https://pdbe.org/3kxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kxu RCSB], [https://www.ebi.ac.uk/pdbsum/3kxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kxu ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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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/kx/3kxu_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=3kxu ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Nucleotide insertions that modify the C terminus of ferritin light chain (FTL) cause neurodegenerative movement disorders named neuroferritinopathies, which are inherited with dominant transmission. The disorders are characterized by abnormal brain iron accumulation. Here we describe the biochemical and crystallographic characterization of pathogenic FTL mutant p.Phe167SerfsX26 showing that it is a functional ferritin with an altered conformation of the C terminus. Moreover we analyze functional and stability properties of ferritin heteropolymers made of 20-23 H-chains and 1-4 L-chains with representative pathogenic mutations or the last 10-28 residues truncated. All the heteropolymers containing the pathogenic or truncated mutants had a strongly reduced capacity to incorporate iron, both when expressed in Escherichia coli, and in vitro when iron was supplied as Fe(III) in the presence of ascorbate. The mutations also reduced the physical stability of the heteropolymers. The data indicate that even a few mutated L-chains are sufficient to alter the permeability of 1-2 of the 6 hydrophobic channels and modify ferritin capacity to incorporate iron. The dominant-negative action of the mutations explains the dominant transmission of the disorder. The data support the hypothesis that hereditary ferritinopathies are due to alterations of ferritin functionality and provide new input on the mechanism of the function of isoferritins.
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===Crystal structure of human ferritin FTL498InsTC pathogenic mutant===
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Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation.,Luscieti S, Santambrogio P, Langlois d'Estaintot B, Granier T, Cozzi A, Poli M, Gallois B, Finazzi D, Cattaneo A, Levi S, Arosio P J Biol Chem. 2010 Apr 16;285(16):11948-57. Epub 2010 Feb 16. PMID:20159981<ref>PMID:20159981</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 3kxu" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20159981}}, adds the Publication Abstract to the page
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*[[Ferritin 3D structures|Ferritin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20159981 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20159981}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Basal ganglia disease, adult-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134790 134790]], Hyperferritinemia-cataract syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134790 134790]]
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==About this Structure==
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3KXU 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=3KXU OCA].
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==Reference==
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<ref group="xtra">PMID:20159981</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arosio, P.]]
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[[Category: Large Structures]]
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[[Category: Estaintot, B Langlois d.]]
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[[Category: Arosio P]]
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[[Category: Gallois, B.]]
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[[Category: Gallois B]]
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[[Category: Granier, T.]]
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[[Category: Granier T]]
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[[Category: Disorder]]
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[[Category: Langlois d'Estaintot B]]
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[[Category: Iron]]
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[[Category: Iron storage protein]]
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[[Category: Metal binding protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 20 08:59:59 2010''
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Current revision

Crystal structure of human ferritin FTL498InsTC pathogenic mutant

PDB ID 3kxu

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