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Who's Afraid of the Big, Bad, Misfolded Protein?
Author(s) -
Murphy M,
Pollnow C,
Misplon M,
Pollen J,
Stack M,
Stack D,
Manogaran A L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb313
Subject(s) - saccharomyces cerevisiae , yeast , sequence (biology) , prion protein , protein aggregation , peptide sequence , protein structure , n terminus , chemistry , translation (biology) , microbiology and biotechnology , biology , computational biology , biophysics , biochemistry , disease , medicine , messenger rna , gene , pathology
Fatal prion diseases, such as Creutzfeldt‐Jakob disease in humans, are associated with the conversion of the normally folded mammalian PrP protein to a misfolded prion form that aggregates. Understanding how prions behave has been greatly facilitated by the study of prions in Saccharomyces cerevisiae, or baker's yeast. In yeast, the translation release factor, Sup35, misfolds to form the [ PSI + ] prion. Although the Sup35 protein has a significantly different primary sequence from PrP, its prion form behaves similarly to human prions. The N‐terminus of Sup35 is Q/N‐rich and responsible for prion formation. Determining the structure of this region has proven difficult since the N‐terminus forms aggregates instead of the ordered crystals required for structural studies. However, a small seven amino acid sequence (GNNQQNY) from Sup35's N‐terminus was crystallized by Nelson et al. (2005). We have constructed a 3D physical model of GNNQQNY as part of the MSOE SMART Teams program using 3D printing technology. GNNQQNY's structure suggests that multiple prion molecules assemble into strong fibrous aggregates through tightly structured interlocking parallel beta sheets called a cross‐β spine. The structure of GNNQQNY suggests a potential model of how human prions assemble, which could potentially help in developing therapies that prevent aggregation. Supported by a grant from NIH‐NCRR‐SEPA .