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Investigating the Effect of the Oligopeptide Repeat Region on Prion Propagation
Author(s) -
Langlois Christine,
Serio Tricia
Publication year - 2012
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.26.1_supplement.752.7
Subject(s) - fungal prion , oligopeptide , prion protein , epigenetics , biology , microbiology and biotechnology , sequence (biology) , phenotype , tandem repeat , biophysics , genetics , chemistry , peptide , biochemistry , genome , gene , medicine , disease , pathology
Prions are proteins that can adopt distinct conformations in vivo : a native form and a collection of misfolded or prion forms, which alter the activity of the protein. Remarkably, the prion forms self‐replicate their structure by assembling into ordered aggregates, which template the conversion of the native form into a like state and allow the associated phenotypes to persist. This process of self‐replication is dictated by the sequence of the prion protein. For example, the Sup35 prion in S. cerevisiae has a bipartite prion domain containing a poly‐glutamine‐rich element and five and a half imperfect repeats of a nonapeptide, which are both required for prion propagation. The polyglutamine region mediates templating, but the function of the repeats is currently unknown. Our studies suggest that the steady‐state size of prion aggregates decreases as repeat number increases, and these effects are exacerbated by the deletion of a newly identified sequence element proximal to the repeats. Intriguingly, changes in aggregate size in either direction decreases the abundance of heritable prion aggregates. Together, our studies suggest that the repeat and proximal regions fine‐tune the process of conformational self‐replication through a change in prion aggregate dynamics to create a protein‐based epigenetic element. Supported by NIH 1F31GM099383‐01.