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Two proposed mode of activation of the HeLo toxicity domain of HET-S.

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posted on 20.02.2013, 04:45 by Sven J. Saupe, Asen Daskalov

The current model envisioned for activation of the HeLo toxicity domain of HET-S is depicted. Upon prion formation, the C-terminal HET-s prion forming domain (PFD) adopts the β-solenoid amyloid fold. The β-solenoid fold of HET-s then serves as a template to transconform the corresponding region in the HET-S protein. Refolding of the HET-S PFD region leads to a refolding of the globular HeLo domain, and this refolding renders the protein toxic. The NWD2 protein displays three domains: an N-terminal motif homologous to the HET-s PFD, a central NACHT oligomerisation domain, and a C-terminal WD-repeat domain (WD). It is proposed that upon binding of a ligand (L), NWD2 undergoes oligomerisation and that this oligomerisation allows the N-terminal region of the NWD2 protein to adopt a HET-s-like β-solenoid fold. This N-terminal extension would then lead to templating and activation of the HET-S HeLo domain (in a way analogous to [Het-s]).


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