PUBLICATION
Quantitative Chemical Proteomics Reveals Interspecies Variations on Binding Schemes of L-FABP with Perfluorooctanesulfonate
- Authors
- Han, J., Fu, J., Sun, J., Hall, D.R., Yang, D., Blatz, D., Houck, K., Ng, C., Doering, J., LaLone, C., Peng, H.
- ID
- ZDB-PUB-210705-7
- Date
- 2021
- Source
- Environmental science & technology 55(13): 9012-9023 (Journal)
- Registered Authors
- Keywords
- dissociation constant, interspecies toxicities, protein folding, proteomics, thermal stability
- MeSH Terms
-
- Alkanesulfonic Acids
- Animals
- Fatty Acid-Binding Proteins
- Fatty Acids
- Fluorocarbons*
- Humans
- Liver
- Mice
- Proteomics*
- Rats
- Species Specificity
- Zebrafish
- PubMed
- 34133149 Full text @ Env. Sci. Tech.
Citation
Han, J., Fu, J., Sun, J., Hall, D.R., Yang, D., Blatz, D., Houck, K., Ng, C., Doering, J., LaLone, C., Peng, H. (2021) Quantitative Chemical Proteomics Reveals Interspecies Variations on Binding Schemes of L-FABP with Perfluorooctanesulfonate. Environmental science & technology. 55(13):9012-9023.
Abstract
Evaluating interspecies toxicity variation is a long-standing challenge for chemical hazard assessment. This study developed a quantitative interspecies thermal shift assay (QITSA) for in situ, quantitative, and modest-throughput investigation of chemical-protein interactions in cell and tissue samples across species. By using liver fatty acid binding protein (L-FABP) as a case study, the QITSA method was benchmarked with six per- and polyfluoroalkyl substances, and thermal shifts (ΔTm) were inversely related to their dissociation constants (R2 = 0.98). The QITSA can also distinguish binding modes of chemicals exemplified by palmitic acid. The QITSA was applied to determine the interactions between perfluorooctanesulfonate (PFOS) and L-FABP in liver cells or tissues from humans, mice, rats, and zebrafish. The largest thermal stability enhancement by PFOS was observed for human L-FABP followed by the mouse, rat, and zebrafish. While endogenous ligands were revealed to partially contribute to the large interspecies variation, recombinant proteins were employed to confirm the high binding affinity of PFOS to human L-FABP, compared to the rat and mouse. This study implemented an experimental strategy to characterize chemical-protein interactions across species, and future application of QITSA to other chemical contaminants is of great interest.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping