IDENTIFICATION OF CANDIDATE PROTEINS BINDING TO PRION PROTEIN

Prion diseases are disorders of protein conformation that produce neur odegeneration in humans and animals. Studies of transgenic (Tg) mice i ndicate that a factor designated protein X is involved in the conversi on of the normal cellular prion protein (PrPc) into the scrapie isofor m (PrPSc); protein X appears to interact with PrPc but not with PrPSc. To search for PrPc binding proteins, we fused PrP with alkaline phosp hatase (AP) to produce a soluble, secreted probe. PrP-AP was used to s creen a lambda gt11 mouse brain cDNA library, and six clones were isol ated. Four cDNAs are novel while two clones are fragments of Nrf2 (NF- ES related factor 2) transcription factor and Aplp1 (amyloid precursor -like protein 1). The observation that PrP binds to a member of the AP P (amyloid precursor protein) gene family is intriguing, in light of p ossible relevance to Alzheimer's disease. Four of the isolated clones are expressed preferentially in the mouse brain and encode a similar m otif. (C) 1997 Academic Press.