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5lg8

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Revision as of 06:55, 31 January 2018

Human L-type ferritin iron loaded for 60 minutes

Structural highlights

5lg8 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	5lg2
Gene:	FTL (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (mu3-oxo)Tris[(mu2-peroxo)(mu2-glutamato-kappaO:kappaO')](glutamato-kappaO)(diaqu o)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin.

Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (mu3-oxo)Tris[(mu2-peroxo)] triiron(III) cluster.,Pozzi C, Ciambellotti S, Bernacchioni C, Di Pisa F, Mangani S, Turano P Proc Natl Acad Sci U S A. 2017 Feb 15. pii: 201614302. doi:, 10.1073/pnas.1614302114. PMID:28202724^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Pozzi C, Ciambellotti S, Bernacchioni C, Di Pisa F, Mangani S, Turano P. Chemistry at the protein-mineral interface in L-ferritin assists the assembly of a functional (mu3-oxo)Tris[(mu2-peroxo)] triiron(III) cluster. Proc Natl Acad Sci U S A. 2017 Feb 15. pii: 201614302. doi:, 10.1073/pnas.1614302114. PMID:28202724 doi:http://dx.doi.org/10.1073/pnas.1614302114

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5lg8"

@@ Line 3: / Line 3: @@
 <StructureSection load='5lg8' size='340' side='right' caption='[[5lg8]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5lg8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LG8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5lg8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LG8 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>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=PER:PEROXIDE+ION'>PER</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5lg2|5lg2]]</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 HUMAN])</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=5lg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lg8 OCA], [http://pdbe.org/5lg8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lg8 RCSB], [http://www.ebi.ac.uk/pdbsum/5lg8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lg8 ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Mangani, S]]
 [[Category: Pisa, F Di]]

5lg8

From Proteopedia

Revision as of 06:55, 31 January 2018

Human L-type ferritin iron loaded for 60 minutes

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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