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Unveiling the binding mode of perfluorooctanoic acid to human serum albumin
Author(s) -
Maso Lorenzo,
Trande Matteo,
Liberi Stefano,
Moro Giulia,
Daems Elise,
Linciano Sara,
Sobott Frank,
Covaceuszach Sonia,
Cassetta Alberto,
Fasolato Silvano,
Moretto Ligia M.,
De Wael Karolien,
Cendron Laura,
Angelini Alessandro
Publication year - 2021
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.4036
Subject(s) - perfluorooctanoic acid , human serum albumin , chemistry , binding site , serum albumin , plasma protein binding , biochemistry
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 sub‐domain 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.