Generating new prions by targeted mutation or segment duplication
Abstract
Prions are self-propagating protein aggregates. We designed rational mutations in four nonprion proteins to examine possible mechanisms for how new prions could evolve. In each case, a small number of mutations were sufficient to cause the proteins to aggregate and, in two cases, to create prion activity. We likewise showed that simply creating tandem repeats of aggregation-prone segments within nonprion proteins can be sufficient to create prion activity, suggesting that such segment duplication may represent a mechanism for generation of new prion domains.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- July 2015
- DOI:
- 10.1073/pnas.1501072112
- Bibcode:
- 2015PNAS..112.8584P