Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides
- Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,
- Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109,
- Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720
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. 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.
- Research Organization:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
- Grant/Contract Number:
- AC02-05CH11231; R01DK073462
- OSTI ID:
- 1235142
- Alternate ID(s):
- OSTI ID: 1512229
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 112 Journal Issue: 33; ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
Similar Records
Engineered Recognition of Tetravalent Zirconium and Thorium by Chelator–Protein Systems: Toward Flexible Radiotherapy and Imaging Platforms
Chelation and stabilization of berkelium in oxidation state +IV