Document Detail


Receptor recognition of transferrin bound to lanthanides and actinides: a discriminating step in cellular acquisition of f-block metals.
MedLine Citation:
PMID:  23446908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Following an internal contamination event, the transport of actinide (An) and lanthanide (Ln) metal ions through the body is facilitated by endogenous ligands such as the human iron-transport protein transferrin (Tf). The recognition of resulting metallo-transferrin complexes (M2Tf) by the cognate transferrin receptor (TfR) is therefore a critical step for cellular uptake of these metal ions. A high performance liquid chromatography-based method has been used to probe the binding of M2Tf with TfR, yielding a direct measurement of the successive thermodynamic constants that correspond to the dissociation of TfR(M2Tf)2 and TfR(M2Tf) complexes for Fe(3+), Ga(3+), La(3+), Nd(3+), Gd(3+), Yb(3+), Lu(3+), (232)Th(4+), (238)UO2(2+), and (242)Pu(4+). Important features of this method are (i) its ability to distinguish both 1 : 1 and 1 : 2 complexes formed between the receptor and the metal-bound transferrin, and (ii) the requirement for very small amounts of each binding partner (<1 nmol of protein per assay). Consistent with previous reports, the strongest receptor affinity is found for Fe2Tf (Kd1 = 5 nM and Kd2 = 20 nM), while the lowest affinity was measured for Pu2Tf (Kd1 = 0.28 μM and Kd2 = 1.8 μM) binding to the TfR. Other toxic metal ions such as Th(IV) and U(VI), when bound to Tf, are well recognized by the TfR. Under the described experimental conditions, the relative stabilities of TfR:(MxTf)y adducts follow the order Fe(3+) >> Th(4+) ~ UO2(2+) ~ Cm(3+) > Ln(3+) ~ Ga(3+) >>> Yb(3+) ~ Pu(4+). This study substantiates a role for Tf in binding lanthanide fission products and actinides, and transporting them into cells by receptor-mediated endocytosis.
Authors:
Gauthier J-P Deblonde; Manuel Sturzbecher-Hoehne; Anne B Mason; Rebecca J Abergel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Metallomics : integrated biometal science     Volume:  5     ISSN:  1756-591X     ISO Abbreviation:  Metallomics     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-03     Completed Date:  2013-12-31     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  101478346     Medline TA:  Metallomics     Country:  England    
Other Details:
Languages:  eng     Pagination:  619-26     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Actinoid Series Elements / chemistry,  metabolism*
Biological Transport
Chromatography, High Pressure Liquid
Lanthanoid Series Elements / chemistry,  metabolism*
Protein Binding
Receptors, Transferrin / metabolism*
Transferrin / chemistry,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 DK 21739/DK/NIDDK NIH HHS; RAI087604Z//PHS HHS; RC2 AI087604/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Actinoid Series Elements; 0/Lanthanoid Series Elements; 0/Receptors, Transferrin; 0/Transferrin
Comments/Corrections

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


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