A Function for the Prion Protein

Protein function is often observed directly following protein isolation, or is deduced by loss of function following gene knockout or by analogy with proteins of known function and similar amino acid sequence. None of these is true in the case of prion proteins because aside from the association with the pathogenesis of the spongiform encaphalopathies, no single obvious function has been described for these molecules until recently. The first two chapters in this volume (see refs. 1 -3 ), concentrated on the characterization of the infectious agent, and led to the introduction of the term “prion” in 1982 (4 ). But it was not until the positive association of the infectious agent, PrPSc, with a normal host gene locus, prnp , that real opportunities to consider protein function in relation to the disease phenotype arose (5 ). The identification of the prion gene on chromosome 2 of the mouse (chromosome 20 in the human) (6 ), and the determination of its sequence (7 ), led to the translation of the encoded protein and speculation concerning its function.