Structural and Biophysical Basis for PFAS Binding by Human Sterol Carrier Protein-2.

Area of Science:

• Environmental Science
• Biochemistry
• Toxicology

Background:

• Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with known adverse health effects.
• PFAS bioaccumulate in human tissues and bind to various lipid-binding proteins (LBPs).
• The full extent of PFAS interaction with LBPs and its role in biological distribution remains unclear.

Purpose of the Study:

• To investigate the interaction between PFAS and human sterol carrier protein 2 (SCP2), a novel LBP candidate.
• To explore the molecular basis of PFAS binding to LBPs.
• To support the hypothesis that a network of LBPs facilitates PFAS distribution and persistence.

Main Methods:

• Screening assays to identify potential PFAS-SCP2 interactions.
• Fluorescence displacement assays to quantify binding affinity.
• Protein structure prediction to model PFAS-SCP2 complexes.
• Nuclear Magnetic Resonance (NMR) experiments to confirm interactions and identify binding sites.

Main Results:

• Sterol carrier protein 2 (SCP2) demonstrates direct binding with various PFAS.
• Key amino acid residues involved in the PFAS-SCP2 interaction were identified.
• The findings provide structural insights into how SCP2 binds to PFAS.

Conclusions:

• SCP2 is identified as a novel PFAS-binding protein.
• This expands the known repertoire of LBPs interacting with PFAS.
• The results support the hypothesis of a distributed LBP network mediating PFAS transport and persistence in humans.