Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Conversion of the cellular isoform of the prion protein (PrP<jats:sup>C</jats:sup>) into the disease-associated isoform (PrP<jats:sup>Sc</jats:sup>) plays a key role in the development of prion diseases. Within its cellular pathway, PrP<jats:sup>C</jats:sup>undergoes several posttranslational modifications, i.e., the attachment of two N-linked glycans and a glycosyl phosphatidyl inositol (GPI) anchor, by which it is linked to the plasma membrane on the exterior cell surface. To study the interaction of PrP<jats:sup>C</jats:sup>with model membranes, we purified posttranslationally modified PrP<jats:sup>C</jats:sup>from transgenic Chinese hamster ovary (CHO) cells. The mono-, di- and oligomeric states of PrP<jats:sup>C</jats:sup>free in solution were analyzed by analytical ultracentrifugation. The interaction of PrP<jats:sup>C</jats:sup>with model membranes was studied using both lipid vesicles in solution and lipid bilayers bound to a chip surface. The equilibrium and mechanism of PrP<jats:sup>C</jats:sup>association with the model membranes were analyzed by surface plasmon resonance. Depending on the degree of saturation of binding sites, the concentration of PrP<jats:sup>C</jats:sup>released from the membrane into aqueous solution was estimated at between 10<jats:sup>-9</jats:sup>and 10<jats:sup>-7</jats:sup> M. This corresponds to a free energy of the insertion reaction of -48 kJ/mol. Consequences for the conversion of PrP<jats:sup>C</jats:sup>to PrP<jats:sup>Sc</jats:sup>are discussed.</jats:p>