Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides

被引:53
作者
Allred, Benjamin E. [1 ]
Rupert, Peter B. [2 ]
Gauny, Stacey S. [1 ]
An, Dahlia D. [1 ]
Ralston, Corie Y. [3 ]
Sturzbecher-Hoehne, Manuel [1 ]
Strong, Roland K. [2 ]
Abergel, Rebecca J. [1 ]
机构
[1] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Chem Sci, Berkeley, CA 94720 USA
[2] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA
[3] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley Ctr Struct Biol, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
actinide transport; siderocalin; protein crystallography; luminescence spectroscopy; antenna effect; DECORPORATION AGENTS; IRON ACQUISITION; IMMUNE-SYSTEM; PROTEIN; PLUTONIUM; BINDING; CARBOXYMYCOBACTINS; SIDEROPHORE; TRANSFERRIN; COMPLEX;
D O I
10.1073/pnas.1508902112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:10342 / 10347
页数:6
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