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PDBsum entry 4zhh
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Metal binding protein/inhibitor
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PDB id
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4zhh
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PDB id:
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| Name: |
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Metal binding protein/inhibitor
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Title:
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Siderocalin-mediated recognition and cellular uptake of actinides
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Structure:
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Neutrophil gelatinase-associated lipocalin. Chain: a, b, c, d, e, f. Fragment: residues 22-198. Synonym: ngal,25 kda alpha-2-microglobulin-related subunit of mmp-9, lipocalin-2,oncogene 24p3,siderocalin lcn2,p25. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: lcn2, hnl, ngal. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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2.04Å
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R-factor:
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0.176
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R-free:
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0.199
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Authors:
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B.E.Allred,P.B.Rupert,S.S.Gauny,D.D.An,C.Y.Ralston,M.Sturzbecher- Hoehne,R.K.Strong,R.J.Abergel
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Key ref:
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B.E.Allred
et al.
(2015).
Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides.
Proc Natl Acad Sci U S A,
112,
10342-10347.
PubMed id:
DOI:
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Date:
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24-Apr-15
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Release date:
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05-Aug-15
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PROCHECK
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Headers
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References
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P80188
(NGAL_HUMAN) -
Neutrophil gelatinase-associated lipocalin from Homo sapiens
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Seq:
Struc:
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198 a.a.
177 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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DOI no:
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Proc Natl Acad Sci U S A
112:10342-10347
(2015)
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PubMed id:
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Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides.
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B.E.Allred,
P.B.Rupert,
S.S.Gauny,
D.D.An,
C.Y.Ralston,
M.Sturzbecher-Hoehne,
R.K.Strong,
R.J.Abergel.
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ABSTRACT
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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.
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Links
