Interaction rule and mechanism of perfluoroalkyl sulfonates containing different carbon chains with human serum albumin

Liu, Yang; Cao, Zhaozhen; Zong, Wansong; Liu, Rutao

doi:10.1039/c7ra02963b

Cited by 19 publications

(22 citation statements)

References 53 publications

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“…While the structure of hSA in complex with PFOA is wider and displays four bound molecules, the structure of hSA in complex with PFOS is more compact and includes only two bound ligands. Similarly to PFOAs, PFOSs occupy FA4 and FA6 pockets and their binding to hSA appear to be exothermic and driven by both polar and non‐polar interactions 34,35 . Yet, the orientations and positions exploited by PFOA and PFOS in FA4 and FA6 pockets differs significantly.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly to PFOAs, PFOSs occupy FA4 and FA6 pockets and their binding to hSA appear to be exothermic and driven by both polar and non-polar interactions. 34,35 Yet, the orientations and positions exploited by PFOA and PFOS in FA4 and FA6 pockets differs significantly. Finally, detailed structural analysis reveals that the greater binding affinity of PFOS toward hSA reported in literature 20,21 could be explained by the presence of an additional oxygen of sulfonate head-group of PFOS and its larger van der Waals volume, which ultimately facilitates the formation of a greater number of intermolecular interactions.…”

Section: Discussionmentioning

confidence: 99%

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Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

et al. 2021

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Perfluorooctanoic acid (PFOA) is a toxic compound that is absorbed and distributed throughout the body by noncovalent binding to serum proteins such as human serum albumin (hSA). Though the interaction between PFOA and hSA has been already assessed using various analytical techniques, a high resolution and detailed analysis of the binding mode is still lacking. We report here the crystal structure of hSA in complex with PFOA and a medium-chain saturated fatty acid (FA). A total of eight distinct binding sites, four occupied by PFOAs and four by FAs, have been identified. In solution binding studies confirmed the 4:1 PFOA-hSA stoichiometry and revealed the presence of one high and three low affinity binding sites. Competition experiments with known hSA-binding drugs allowed locating the high affinity binding site in subdomain IIIA. The elucidation of the molecular basis of the interaction between PFOA and hSA might provide not only a better assessment of the absorption and elimination mechanisms of these compounds in vivo but also have implications for the development of novel molecular receptors for diagnostic and biotechnological applications. K E Y W O R D S binding mode, crystal structure, fluoroalkyl substances, human serum albumin, molecular interaction, perfluorooctanoic acid 1 | INTRODUCTION Perfluorooctanoic acid (PFOA) is a perfluoroalkyl substance (PFAS) with a carboxyl functional group and seven fluorinated carbon atoms. 1 PFOA is a man-made

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

et al. 2021

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“…We found that PFOS bound Der p1 with dissociation constant at equilibrium (K d ) = 224 nM, compared with albumin, K d = 80 nM, and the PFOS-liver fatty acid binding protein complex (K d = 2,099 nM) (46,47). In children with the highest serum concentrations of PFOS (207 nM), exposure to PFOS at nanomolar concentrations significantly inhibits human serum albumin and liver fatty acid binding protein in vitro (48,49). These results suggest that investigators should focus on the potency of PFOS and how it influences the allergenic effects of HDM in humans.…”

Section: Discussionmentioning

confidence: 96%

Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma

Wang

Hou

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Allergic asthma, driven by T helper 2 cell-mediated immune responses to common environmental antigens, remains the most common respiratory disease in children. Perfluorinated chemicals (PFCs) are environmental contaminants of great concern, because of their wide application, persistence in the environment, and bioaccumulation. PFCs associate with immunological disorders including asthma and attenuate immune responses to vaccines. The influence of PFCs on the immunological response to allergens during childhood is unknown. We report here that a major PFC, perfluorooctane sulfonate (PFOS), inactivates house dust mite (HDM) to dampen 5-wk-old, early weaned mice from developing HDM-induced allergic asthma. PFOS further attenuates the asthma protective effect of the microbial product lipopolysaccharide (LPS). We demonstrate that PFOS prevents desensitization of lung epithelia by LPS, thus abolishing the latter’s protective effect. A close mechanistic study reveals that PFOS specifically binds the major HDM allergen Der p1 with high affinity as well as the lipid A moiety of LPS, leading to the inactivation of both antigens. Moreover, PFOS at physiological human (nanomolar) concentrations inactivates Der p1 from HDM and LPS in vitro, although higher doses did not cause further inactivation because of possible formation of PFOS aggregates. This PFOS-induced neutralization of LPS has been further validated in primary human cell models and extended to an in vivo bacterial infection mouse model. This study demonstrates that early life exposure of mice to a PFC blunts airway antigen bioactivity to modulate pulmonary inflammatory responses, which may adversely affect early pulmonary health.

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“…20 For instance, PFOA and PFOS affinity towards serum proteins such as albumin and haemoglobin was extensively characterised by multi-analytical approaches based on fluorescence spectroscopy, mass spectrometry (MS), circular dichroism, isothermal titration calorimetry, X-ray crystallography, and molecular docking. [21][22][23][24] Multi-analytical studies confirmed the strong affinity of PFOA for human serum albumin (hSA): PFOA's carboxylate head and fluorinated C8 tail mimic the structure of fatty acids promoting PFOA binding into hSA's hydrophobic pockets. 25,26 Similarly to fatty acids, hSA-PFOA interactions are non-covalent, mainly hydrophobic, and influenced by protein conformation and environmental conditions (such as pH).…”

Section: Introductionmentioning

confidence: 92%

Native mass spectrometry for the design and selection of protein bioreceptors for perfluorinated compounds

Daems

Moro

Berghmans

et al. 2021

Analyst

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Interaction rule and mechanism of perfluoroalkyl sulfonates containing different carbon chains with human serum albumin

Abstract: All three PFASs bind to HSA mainly through electrostatic forces and the toxicity decreases with the shortening of the carbon chain.

Cited by 19 publications

References 53 publications

Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma

Native mass spectrometry for the design and selection of protein bioreceptors for perfluorinated compounds

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