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Zachery Deckner, Pavithra Chandramowlishwaran, Meng Sun, Denis Kiktev and Yury O Chernoff
Georgia Institute of Technology, USA
Posters & Accepted Abstracts: Microbiol Biotechnol Rep
Amyloid proteins (including transmissible amyloids, prions) cause heritable, sporadic and infectious diseases in humans. Formation of the amyloid fibril is postulated to occur through a two-step process. First, the normal soluble protein is converted into small aggregates or nuclei of the prion isoform of that protein by a process called nucleation. Second, these nuclei seed the conversion of protein molecules containing the same or similar amino acid sequence thereby sequestering them into long fibrils. A similar molecular mechanism is employed by yeast prions, which are not homologous to known mammalian amyloid and prion proteins by sequence, and control heritable traits. We have developed a yeast-based assay that allows us to study the initial nucleation mechanism of any mammalian amyloidogenic protein. Here, we show that chimeric proteins composed of Sup35 fragments, including prion-forming domain and fused to aggregation-prone regions of mammalian prion protein (PrP), human amyloid beta (associated with Alzheimerâ��s disease), human �±-synuclein (associated with Parkinsonâ��s disease), human amylin (associated with type II diabetes), or the M-region of tumor suppressor protein 53 (associated with many forms of cancer), nucleate new Sup35 prions even in the absence of of the Rnq1 prion or any other pre-existing nuclei. Our data indicate that prion/amyloid properties of mammalian amyloidogenic proteins that are detected in yeast and mammalian (or in vitro) systems are controlled by the same sequence elements.
Zachery Deckner has completed his BS in Biology from GCSU and is currently a PhD student at Georgia Tech. He is working on identifying and studying new amyloidogenic proteins implicated in various proteopathies. He has mentored undergraduuate students and wants to take up a teaching career after his graduation.
