Yeast prion protein New1 can break Sup35 amyloid fibrils into fragments in an ATP-dependent manner.

We report a new type of interaction between two yeast prion proteins, Sup35 and New1. New1 consists of an N-terminal prion region (New1N) and a C-terminal region homologous to a translation elongation factor with two ATP-binding motifs. Amyloid formation of the Sup35 prion region (Sup35NM) was accelerated by a small amount of sonicated New1N amyloid (New1N-seeds) to produce Sup35NM[New1] amyloid. New1N amyloid formation was accelerated by Sup35NM[New1]-seeds but not by spontaneously generated Sup35NM-seeds, indicating that the structural features of the New1N amyloid were transmitted via the Sup35NM amyloid. Surprisingly, full-length New1 broke the Sup35NM amyloid fibrils in an ATP-dependent manner. This activity of New1 was independent from Hsp104. It was lost by a mutation in the second ATP-binding motif, by the truncation of the N-terminal prion region of New1 and by the pre-incubation of New1 with New1N-seeds. When New1 was overproduced in yeast [PSI(+)] cells carrying GFP-fused Sup35NM, diverse morphological changes in fluorescent foci occurred. Thus, New1 potentially has a regulatory role in prion state in yeast, working independently of the Hsp104 system.