Shadoo binds lipid membranes and undergoes aggregation and fibrillization

•Shadoo is monomeric disordered protein at acidic pH, but aggregates at pH⩾7.•Shadoo binds anionic lipid vesicles.•Shadoo destabilizes negatively charged membranes.•Sho bound to an anionic lipid surface can assembly into fibrillar structures. Lipid membrane can enhance prion protein (PrP) pathological fibrillogenesis. A neuronal paralog of PrP, named Shadoo (Sho), is localized to similar membrane environment as PrP and can also convert to amyloid-like fibrilles. To gain insight into the role of Sho in prion diseases, we studied Sho interactions with cellular membrane models. Sho was found to bind anionic lipid vesicles. Spectroscopic and microscopic data showed that membrane-associated Sho slowly converted into amyloid fibers. Furthermore, binding of Sho to anionic liposomes has a disruptive effect on the integrity of the lipid bilayer leading to the formation of supramolecular lipid–protein complexes. In consequence, the role of Sho in prion diseases might depend on the oligomerization state of Sho but also the nature of these lipoprotein assembles.