NR AQKJ
AU Hara,H.; Nakayashiki,T.; Crist,C.G.; Nakamura,Y.
TI Prion domain interaction responsible for species discrimination in yeast [PSI+] transmission
QU Genes to Cells : devoted to molecular & cellular mechanisms 2003 Dec; 8(12): 925-39
PT journal article
AB BACKGROUND: The yeast [PSI+] factor is transmitted by a prion mechanism involving self-propagating Sup35 aggregates. As with mammalian prions, a species barrier prevents prion transmission between yeast species. The N-terminal of Sup35 of Saccharomyces cerevisiae, necessary for [PSI+], contains two species-signature elements-a Gln/Asn-rich region (residues 1-41; designated NQ) that is followed by oligopeptide repeats (designated NR). RESULTS: In this study, we show that S. cerevisiae[PSI+] is transmissible through plasmid shuffling and cytoplasmic transfer to heterotypic Sup35s whose NQ is replaced with the S. cerevisiae NQ. In addition to homology, the N-terminal location is essential for NQ mediated susceptibility to [PSI+] transmission amongst heterotypic Sup35s. In vitro, a swap of NQ of S. cerevisiae Sup35 led to cross seeding of amyloid formation. CONCLUSIONS: These findings suggest that NQ discriminates self from non-self, and is sufficient to initiate [PSI+] transmission irrespective of whether NR is heterotypic. NR as well as NQ alone coalesces into existing [PSI+] aggregates, showing their independent potentials to interact with the identical sequence in the [PSI+] conformer. The role of NQ and NR in [PSI+] prion formation is discussed.
MH Amino Acid Sequence; Chimeric Proteins/chemistry; Molecular Sequence Data; Mutation; Peptides/chemistry; Plasmids; Prion Diseases/transmission; Prions/*chemistry/genetics; Protein Structure, Tertiary; Saccharomyces cerevisiae/genetics/growth & development; Saccharomyces cerevisiae Proteins/*chemistry/genetics; Species Specificity; Support, Non-U.S. Gov't
AD Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
SP englisch
PO England