title: Screening of human serum proteins for uranium binding.
abstract: About 20% of uranyl ions in serum are associated with the protein pool. A few of them such as transferrin have been characterized, but most still have to be identified to obtain a better explanation of the biochemical toxicology and kinetics of uranium. We designed an in vitro sensitive procedure involving a combination of bidimensional chromatography with time-resolved fluorescence, coupled with proteomic analysis, to identify uranium-binding proteins in human serum fractions. Ten novel targets were identified and validated using purified proteins and inductively coupled plasma mass spectrometry. Of these, ceruloplasmin, hemopexin, and two complement proteins displayed the capacity to bind uranium with stoichiometry greater than 1 mole of uranium per mole of protein. Not all of these targets are metalloproteins, suggesting that uranyl ions can use a wide variety of binding sites and coordination strategies. These data provide additional insights into a better understanding of uranium chemical toxicity.
authors.affiliation: CEA/VALRHO-Marcoule, Service de Biochimie Post-génomique et de Toxicologie Nucléaire (DSV-DIEP), Bagnols sur Cèze 30207, France. claude.vidaud@cea.fr
authors.forename: Claude
authors.initials: C
authors.lastname: Vidaud
authors.forename: Alain
authors.initials: A
authors.lastname: Dedieu
authors.forename: Christian
authors.initials: C
authors.lastname: Basset
authors.forename: Sophie
authors.initials: S
authors.lastname: Plantevin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dany
authors.forename: Olivier
authors.initials: O
authors.lastname: Pible
authors.forename: Eric
authors.initials: E
authors.lastname: Quéméneur
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014501:Uranium / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D014501:Uranium