Stabilisation of Active Form of Natural Human PON1 Requires HPBP

Human PON1 displays functional promiscuity correlated to its natural biological milieu. Devoid of its physiological HDL environment, the natural human enzyme is unstable. The serendipitous discovery of HPBP, a PON1 partner protein, and the contamination of current PON1 preparations causing misinterpretation of PON1’s functions are central new data. Besides, both activities and stability of PON1 are completely dependent on the HDL components’ molecular surrounding. Because of the variability of the HDL environment of PON1, identification of partner lipoprotein(s) or/and hydrophobic cofactor(s) capable of acting as reliable surrogate stabilizer(s) of the enzyme’s functional conformation is crucial. Attempts at characterizing PON1’s functional state(s), determining its thermal stability and describing factors involved in its storage stability demonstrated that HPBP helps to stabilize the active form(s) of natural human PON1. Together with the depiction of other HDL-associated components in the modulation of PON1 stability, these data shed light on the contribution of the HDL environment to the interactions of PON1 with its natural and/or multiples substrates