View source for 4zhg


==Siderocalin-mediated recognition and cellular uptake of actinides==
<StructureSection load='4zhg' size='340' side='right'caption='[[4zhg]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zhg]] is a 6 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=4ZHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZHG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4OL:N,N-BUTANE-1,4-DIYLBIS[1-HYDROXY-N-(3-{[(1-HYDROXY-6-OXO-1,6-DIHYDROPYRIDIN-2-YL)CARBONYL]AMINO}PROPYL)-6-OXO-1,6-DIHYDROPYRIDINE-2-CARBOXAMIDE]'>4OL</scene>, <scene name='pdbligand=AM:AMERICIUM+ION'>AM</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4zhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zhg OCA], [https://pdbe.org/4zhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zhg RCSB], [https://www.ebi.ac.uk/pdbsum/4zhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zhg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NGAL_HUMAN 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.<ref>PMID:12453413</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Synthetic radionuclides, such as the transuranic actinides plutonium, americium, and curium, present severe health threats as contaminants, and understanding the scope of the biochemical interactions involved in actinide transport is instrumental in managing human contamination. Here we show that siderocalin, a mammalian siderophore-binding protein from the lipocalin family, specifically binds lanthanide and actinide complexes through molecular recognition of the ligands chelating the metal ions. Using crystallography, we structurally characterized the resulting siderocalin-transuranic actinide complexes, providing unprecedented insights into the biological coordination of heavy radioelements. In controlled in vitro assays, we found that intracellular plutonium uptake can occur through siderocalin-mediated endocytosis. We also demonstrated that siderocalin can act as a synergistic antenna to sensitize the luminescence of trivalent lanthanide and actinide ions in ternary protein-ligand complexes, dramatically increasing the brightness and efficiency of intramolecular energy transfer processes that give rise to metal luminescence. Our results identify siderocalin as a potential player in the biological trafficking of f elements, but through a secondary ligand-based metal sequestration mechanism. Beyond elucidating contamination pathways, this work is a starting point for the design of two-stage biomimetic platforms for photoluminescence, separation, and transport applications.

Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides.,Allred BE, Rupert PB, Gauny SS, An DD, Ralston CY, Sturzbecher-Hoehne M, Strong RK, Abergel RJ Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10342-7. doi:, 10.1073/pnas.1508902112. Epub 2015 Aug 3. PMID:26240330<ref>PMID:26240330</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zhg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]]
*[[Siderocalin 3D structures|Siderocalin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abergel RJ]]
[[Category: Allred BE]]
[[Category: An DD]]
[[Category: Gauny SS]]
[[Category: Ralston CY]]
[[Category: Rupert PB]]
[[Category: Strong RK]]
[[Category: Sturzbecher-Hoehne M]]