NR AQZF
AU Ross,E.D.; Baxa,U.; Wickner,R.B.
TI Scrambled prion domains form prions and amyloid
QU Molecular and Cellular Biology 2004 Aug; 24(16): 7206-13
PT journal article
AB The [URE3] prion of Saccharomyces cerevisiae is a self-propagating amyloid form of Ure2p. The amino-terminal prion domain of Ure2p is necessary and sufficient for prion formation and has a high glutamine (Q) and asparagine (N) content. Such Q/N-rich domains are found in two other yeast prion proteins, Sup35p and Rnq1p, although none of the many other yeast Q/N-rich domain proteins have yet been found to be prions. To examine the role of amino acid sequence composition in prion formation, we used Ure2p as a model system and generated five Ure2p variants in which the order of the amino acids in the prion domain was randomly shuffled while keeping the amino acid composition and C-terminal domain unchanged. Surprisingly, all five formed prions in vivo, with a range of frequencies and stabilities, and the prion domains of all five readily formed amyloid fibers in vitro. Although it is unclear whether other amyloid-forming proteins would be equally resistant to scrambling, this result demonstrates that [URE3] formation is driven primarily by amino acid composition, largely independent of primary sequence.
MH *Amino Acid Sequence; Amino Acids/chemistry; Amyloid/chemistry/*genetics/metabolism/ultrastructure; Human; Molecular Sequence Data; Prions/chemistry/*genetics/metabolism/ultrastructure; Protein Conformation; Protein Structure, Tertiary; Random Allocation; Saccharomyces cerevisiae/genetics/*metabolism; Saccharomyces cerevisiae; Proteins/chemistry/*genetics/metabolism/ultrastructure; Sequence Alignment
AD Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA
SP englisch
PO USA