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Title: Chemoproteomic Approach toward Probing the Interactomes of Perfluoroalkyl Substances.

Authors: Zhang, Quanqing; Dong, Xuejiao; Lu, Jiuwei; Song, Jikui; Wang, Yinsheng

Published In Anal Chem, (2021 Jul 13)

Abstract: Poly- and perfluoroalkyl substances (PFASs) are widely used in industrial products and consumer goods. Due to their extremely recalcitrant nature and potential bioaccumulation and toxicity, exposure to PFASs may result in adverse health outcomes in humans and wildlife. In this study, we developed a chemoproteomic strategy, based on the use of isotope-coded desthiobiotin-perfluorooctanephosphonic acid (PFOPA) probe and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, to profile PFAS-binding proteins. Targeted proteins were labeled with the desthiobiotin-PFOPA probe, digested with trypsin, and the ensuing desthiobiotin-conjugated peptides were enriched with streptavidin beads for LC-MS/MS analysis. We were able to identify 469 putative PFOPA-binding proteins. By conducting competitive binding experiments using low (10 μM) and high (100 μM) concentrations of stable isotope-labeled PFOPA probes, we further identified 128 nonredundant peptides derived from 75 unique proteins that exhibit selective binding toward PFOPA. Additionally, we demonstrated that one of these proteins, fatty acid-binding protein 5 (FABP5), could interact directly with PFASs, including perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), and perfluorobutanesulfonic acid (PFBS). Furthermore, desthiobiotin-labeled lysine residues are located close to the fatty acid-binding pocket of FABP5, and the binding affinity varies with the structures of PFASs. Taken together, we developed a novel chemoproteomic method for interrogating the PFAS-interacting proteome. The identification of these proteins sets the stage for understanding the mechanisms through which exposure to PFASs confers adverse human health effects.

PubMed ID: 34185510 Exiting the NIEHS site

MeSH Terms: Alkanesulfonic Acids*; Chromatography, Liquid; Environmental Pollutants; Fatty Acid-Binding Proteins; Fluorocarbons*; Humans; Proteome*; Tandem Mass Spectrometry

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