Mammalian Prion Protein.

The discoveries of prion disease transmission in mammals and a non-Mendelian type of inheritance in yeast has led to the establishment of a new concept in biology, "the prion hypothesis." This hypothesis postulates that an abnormal protein conformation propagates itself in an autocatalytic manner by recruiting the cellular isoform of the same protein, and, therefore, acts either as transmissible agent of disease (in mammals) or as heritable determinant of phenotype (in yeast and fungus). While the prion biology of yeast and fungus supports this idea strongly, the direct proof of the "protein-only" hypothesis in mammals, the generation of PrPScin vitro, de novo from noninfectious PrP, has been difficult to achieve despite many years of effort. The current review discusses potential strategies for generation of prion infectivity de novo and summarizes our current knowledge about biophysical mechanisms of prion conversion. [ABSTRACT FROM AUTHOR]