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Employing the Sequence Alignment to Predict Across Species Susceptibility tool to inform bioaccumulation potential of per- and polyfluorinated alkyl substances across species
Citation:
Lalone, C., J. Doering, W. Cheng, H. Peng, AND C. Ng. Employing the Sequence Alignment to Predict Across Species Susceptibility tool to inform bioaccumulation potential of per- and polyfluorinated alkyl substances across species. SETAC North America, Toronto, ON, CANADA, November 03 - 07, 2019.
Impact/Purpose:
Per and polyfluoroalkyl substances (PFAS) are a group of chemicals that have been widely used in industrial and consumer products and found in the environment. It is known that these substances can bioaccumulate, however there are limited data regarding their ability bioaccumulate across the diversity of species. PFAS are known to interact with certain proteins in mammals thought to be involved in their bioaccumulation potential. Therefore, understanding if these proteins are found in other organisms can provide an initial indication of whether PFAS have the potential to interact with the protein in another species and bioaccumulate. The US EPA Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS) was used in this initial study to understand how and if PFAS are likely to interact with the liver fatty acid binding protein in other species to inform follow up cross species bioaccumulation studies.
Description:
Perfluorinated alkylated substances (PFAS) are synthetic chemicals used in a variety of industrial applications and consumer products, notably fire-fighting foams and cleaning materials. Due to the ubiquitous nature of PFAS in the environment, they have been measured in tissues from species as diverse as whales, birds, fish, and even invertebrates, covering a range of trophic levels. The ability of these chemicals to bioaccumulate is largely due to protein binding, with both serum albumin in the blood and fatty acid binding proteins in the liver capable of important interactions. Due to the involvement of proteins in bioaccumulation, the US Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was used to evaluate protein conservation and predict similarities and differences in bioaccumulation potential across species that could be used for advanced in silico and chemical proteomic evaluations. Level 1 of SeqAPASS compared human primary amino acid sequences for serum albumin and liver fatty acid binding protein (LFABP) to all other protein sequences that exist in publicly available protein databases. These results provide a line of evidence that serum albumin and LFABP are conserved across the majority of vertebrate species. And due to knowledge of amino acid residues identified as critical for the interaction of PFAS with LFABP, Level 3 of SeqAPASS was used to compare individual amino acids. From these results, two positions, 50 and 94, were identified as potentially important for differences in PFAS bioaccumulation due to the differences observed when comparing across taxonomic groups. For example, a substitution of phenylalanine at position 93 for threonine predicted that zebrafish may differ from human LFABP in interactions with PFOS therefore leading to potential differences in bioaccumulation. Overall, results from SeqAPASS were used to guide molecular homology modeling and molecular dynamics simulations to further evaluate species similarities and differences to predict potential for bioaccumulation of PFAS across species. Cross-species chemical proteomic studies will be used to confirm and expand upon in silico results.