Structure-Based Investigation on the Interaction of Perfluorinated Compounds with Human Liver Fatty Acid Binding Protein
Abstract
Perfluorinated compounds (PFCs) are known to accumulate in liver and induce hepatotoxicity on experimental animals. Liver fatty acid binding protein (L-FABP) is expressed highly in hepatocytes and binds fatty acids. PFCs may bind with FABP and change their ADME and toxicity profile. In the present study, the binding interaction of 17 structurally diverse PFCs with human L-FABP was investigated to assess their potential disruption effect on fatty acid binding. The binding affinity of twelve perfluorinated carboxylic acids (PFCAs), as determined by fluorescence displacement assay, increased significantly with their carbon number from 4 to 11, and decreased slightly when the number was over 11. The three perfluorinated sulfonic acids (PFSAs) displayed comparable affinity, but no binding was detected for the two fluorotelomer alcohols. Circular dichroism results showed that PFC binding induced distinctive structural changes of the protein. Molecular docking revealed that the driving forces for the binding of PFCs with FABP were predominantly hydrophobic and hydrogen-bonding interactions, and the binding geometry was dependent on both the size and rigidity of the PFCs. Based on the binding constant obtained in this work, the possibility of in vivo competitive displacement of fatty acids from FABP by PFCs was estimated.
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PFCAs with carbon chain lengths between 10 and 15 may bind to serum proteins and cross the blood-brain barrier in a similar way to saturated fatty acids.
“hypothesizing that PFCAs with carbon chain lengths between 10 and 15 may be binding to serum proteins and crossing the BBB in a similar way to saturated fatty acids.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Zhang et al., 2013
In vitro work demonstrates that proteins like human serum albumin and human L-FABP have optimal affinity for PFAS with carbon chain length around 10.
“This hypothesis is supported by in vitro work demonstrating that proteins like human serum albumin and human L-FABP have optimal affinity for PFAS with carbon chain length around 10 (Zhang et al., 2013; Jackson et al., 2021).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Zhang et al., 2013
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- Authors
- Zhang, L., Ren, X.-M., & Guo, L.-H.
- Affiliations
- Chinese Academy of Sciences (CN)
- Chinese Academy of Sciences , , P.O. Box 2871, 18 Shuangqing Road , Beijing 100085 ,
- Corresponding author
- Guo, Liang-Hong
- Venue
- Environmental Science & Technology
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-09-05
- Volume
- 47
- Issue
- 19
- Pages
- 11293-11301
- ISSN
- 0013-936X (ISSN-L)
- 1520-5851
- OpenAlex
- W2332969818
- Cited by
- 267
- References
- 54
- Citations by year
- 2026: 38 · 2025: 37 · 2024: 23 · 2023: 33 · 2022: 23 · 2021: 24 · 2020: 27 · 2019: 21 · 2018: 11 · 2017: 12 · 2016: 5 · 2015: 5 · 2014: 8
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Environmental Science & Technology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- perfluorinated compounds, liver fatty acid binding protein, perfluorinated carboxylic acids, perfluorinated sulfonic acids, fluorotelomer alcohols, protein-ligand binding, binding affinity, protein conformational change, hepatotoxicity, carbon chain length effect, hydrophobic interactions, hydrogen bonding
- MeSH terms
- Fatty Acids, Fluorocarbons, Humans, Alkanesulfonic Acids, Fatty Acid-Binding Proteins
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