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Perfluoroalkyl Acid Binding with Peroxisome Proliferator-Activated Receptors α, γ, and δ, and Fatty Acid Binding Proteins by Equilibrium Dialysis with a Comparison of Methods
- Source :
- Toxics; Volume 9; Issue 3; Pages: 45, Toxics, Toxics, Vol 9, Iss 45, p 45 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- The biological impacts of per- and polyfluorinated alkyl substances (PFAS) are linked to their protein interactions. Existing research has largely focused on serum albumin and liver fatty acid binding protein, and binding affinities determined with a variety of methods show high variability. Moreover, few data exist for short-chain PFAS, though their prevalence in the environment is increasing. We used molecular dynamics (MD) to screen PFAS binding to liver and intestinal fatty acid binding proteins (L- and I-FABPs) and peroxisome proliferator activated nuclear receptors (PPAR-α, -δ and -γ) with six perfluoroalkyl carboxylates (PFCAs) and three perfluoroalkyl sulfonates (PFSAs). Equilibrium dissociation constants, KDs, were experimentally determined via equilibrium dialysis (EqD) with liquid chromatography tandem mass spectrometry for protein-PFAS pairs. A comparison was made between KDs derived from EqD, both here and in literature, and other in vitro approaches (e.g., fluorescence) from literature. EqD indicated strong binding between PPAR-δ and perfluorobutanoate (0.044 ± 0.013 µM) and perfluorohexane sulfonate (0.035 ± 0.0020 µM), and between PPAR-α and perfluorohexanoate (0.097 ± 0.070 µM). Unlike binding affinities for L-FABP, which increase with chain length, KDs for PPARs showed little chain length dependence by either MD simulation or EqD. Compared with other in vitro approaches, EqD-based KDs consistently indicated higher affinity across different proteins. This is the first study to report PPARs binding with short-chain PFAS with KDs in the sub-micromolar range.
- Subjects :
- Stereochemistry
Health, Toxicology and Mutagenesis
Serum albumin
010501 environmental sciences
Toxicology
lcsh:Chemical technology
01 natural sciences
Fatty acid-binding protein
Article
Protein–protein interaction
03 medical and health sciences
chemistry.chemical_compound
Liquid chromatography–mass spectrometry
lcsh:TP1-1185
Receptor
equilibrium dialysis
peroxisome proliferator-activated receptors
fatty acid-binding proteins
per- and polyfluorinated alkyl substances
equilibrium dissociation constants
030304 developmental biology
0105 earth and related environmental sciences
0303 health sciences
Chemical Health and Safety
biology
In vitro
Dissociation constant
Sulfonate
chemistry
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 23056304
- Database :
- OpenAIRE
- Journal :
- Toxics; Volume 9; Issue 3; Pages: 45
- Accession number :
- edsair.doi.dedup.....a0ffbc54740b051d1e7d7ce7e14511bd
- Full Text :
- https://doi.org/10.3390/toxics9030045