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5jr8

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Revision as of 11:34, 17 June 2020

Disposal of Iron by a Mutant form of Siderocalin NGAL

Structural highlights

5jr8 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	LCN2, HNL, NGAL (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NGAL_HUMAN] Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.^[1]

Publication Abstract from PubMed

Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe-/-) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway.

Disposal of iron by a mutant form of lipocalin 2.,Barasch J, Hollmen M, Deng R, Hod EA, Rupert PB, Abergel RJ, Allred BE, Xu K, Darrah SF, Tekabe Y, Perlstein A, Wax R, Bruck E, Stauber J, Corbin KA, Buchen C, Slavkovich V, Graziano J, Spitalnik SL, Bao G, Strong RK, Qiu A Nat Commun. 2016 Oct 31;7:12973. doi: 10.1038/ncomms12973. PMID:27796299^[2]

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

References

↑ Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002 Nov;10(5):1045-56. PMID:12453413
↑ Barasch J, Hollmen M, Deng R, Hod EA, Rupert PB, Abergel RJ, Allred BE, Xu K, Darrah SF, Tekabe Y, Perlstein A, Wax R, Bruck E, Stauber J, Corbin KA, Buchen C, Slavkovich V, Graziano J, Spitalnik SL, Bao G, Strong RK, Qiu A. Disposal of iron by a mutant form of lipocalin 2. Nat Commun. 2016 Oct 31;7:12973. doi: 10.1038/ncomms12973. PMID:27796299 doi:http://dx.doi.org/10.1038/ncomms12973

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jr8"

@@ Line 1: / Line 1: @@
 ==Disposal of Iron by a Mutant form of Siderocalin NGAL==
-<StructureSection load='5jr8' size='340' side='right' caption='[[5jr8]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+<StructureSection load='5jr8' size='340' side='right'caption='[[5jr8]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jr8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JR8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jr8]] is a 2 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=5JR8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JR8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=5jr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jr8 OCA], [http://pdbe.org/5jr8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jr8 RCSB], [http://www.ebi.ac.uk/pdbsum/5jr8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jr8 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LCN2, HNL, NGAL ([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://proteopedia.org/fgij/fg.htm?mol=5jr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jr8 OCA], [http://pdbe.org/5jr8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jr8 RCSB], [http://www.ebi.ac.uk/pdbsum/5jr8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jr8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5jr8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]]
+*[[Siderocalin|Siderocalin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Abergel, R]]
 [[Category: Allred, B]]

5jr8

From Proteopedia

Revision as of 11:34, 17 June 2020

Disposal of Iron by a Mutant form of Siderocalin NGAL

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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