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The mechanism of prion inhibition by HET-S.
- Source :
-
Molecular cell [Mol Cell] 2010 Jun 25; Vol. 38 (6), pp. 889-99. - Publication Year :
- 2010
-
Abstract
- HET-S (97% identical to HET-s) has an N-terminal globular domain that exerts a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation. We show that HET-S fails to form fibrils in vitro and that it inhibits HET-s PFD fibrillization in trans. In vivo analyses indicate that beta-structuring of the HET-S PFD is required for HET-S activity. The crystal structures of the globular domains of HET-s and HET-S are highly similar, comprising a helical fold, while NMR-based characterizations revealed no differences in the conformations of the PFDs. We conclude that prion inhibition is not encoded by structure but rather in stability and oligomerization properties: when HET-S forms a prion seed or is incorporated into a HET-s fibril via its PFD, the beta-structuring in this domain induces a change in its globular domain, generating a molecular species that is incompetent for fibril growth.<br /> (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 38
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 20620958
- Full Text :
- https://doi.org/10.1016/j.molcel.2010.05.019