SELF-SEEDED FIBERS FORMED BY SUP35, THE PROTEIN DETERMINANT OF [PSI-LIKE FACTOR OF SACCHAROMYCES-CEREVISIAE(], A HERITABLE PRION)

The [PSI+] factor of S. cerevisiae represents a new form of inheritanc e: cytosolic transmission of an altered phenotype is apparently based upon inheritance of an altered protein structure rather than an altere d nucleic acid. The molecular basis of its propagation is unknown. We report that purified Sup35 and subdomains that induce [PSI+] elements in vivo form highly ordered fibers in vitro. Fibers bind Congo red and are rich in beta sheet, characteristics of amyloids found in certain human diseases, including the prion diseases. Some fibers have distinc t structures and these, once initiated, are self-perpetuating. Preform ed fibers greatly accelerate fiber formation by unpolymerized protein. These data support a ''protein-only'' seeded polymerization model for the inheritance of [PSI+].