Synthetic Anchored Prion Protein Created

Researchers have synthesized prion proteins linked to glycosylphosphatidylinositol (GPI), a sugar-lipid that attaches proteins to cell membranes. The construct is the first fully synthetic GPI-anchored protein ever made. The work should ease the synthesis of other anchored proteins and aid mechanistic studies of prion disease. Prion protein can become infectious and cause mad cow disease in cattle and Creutzfeldt-Jakob disease in people, but the disease mechanism is unknown. GPI anchoring to cell membranes plays a crucial role in the structural change by which prion protein converts to an infectious form, but scientists have not been able to prepare sufficient amounts of homogeneous anchored prion protein from natural sources to study the process. Christian F. W. Becker of the Technical University of Munich; Peter H. Seeberger of the Swiss Federal Institute of Technology, in Zurich; and coworkers produced prion protein in bacteria and used native chemical ligation to link it to a GPI anchor they synthesized separately (Angew. Chem. Int. Ed. 2008, 47, 8215). The protein-anchor complex isn't a fully faithful replica of its natural counterpart because cysteine-thioester chemistry is needed to combine the two units, but it's close.