Saibil, Helen R. and Seybert, A. and Habermann, A. and Winkler, J. and Eltsov, M. and Perkovic, M. and Castano-Diez, D. and Scheffer, M.P. and Haselmann, U. and Chlanda, P. and Lindquist, S. and Tyedmers, J. and Frangakis, A.S. (2012) Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures. Proceedings of the National Academy of Sciences of the United States of America 109 (37), pp. 14906-14911. ISSN 0027-8424.
Abstract
Yeast prions constitute a “protein-only” mechanism of inheritance that is widely deployed by wild yeast to create diverse phenotypes. One of the best-characterized prions, [PSI+], is governed by a conformational change in the prion domain of Sup35, a translation-termination factor. When this domain switches from its normal soluble form to an insoluble amyloid, the ensuing change in protein synthesis creates new traits. Two factors make these traits heritable: (i) the amyloid conformation is self-templating; and (ii) the protein-remodeling factor heat-shock protein (Hsp)104 (acting together with Hsp70 chaperones) partitions the template to daughter cells with high fidelity. Prions formed by several other yeast proteins create their own phenotypes but share the same mechanistic basis of inheritance. Except for the amyloid fibril itself, the cellular architecture underlying these protein-based elements of inheritance is unknown. To study the 3D arrangement of prion assemblies in their cellular context, we examined yeast [PSI+] prions in the native, hydrated state in situ, taking advantage of recently developed methods for cryosectioning of vitrified cells. Cryo–electron tomography of the vitrified sections revealed the prion assemblies as aligned bundles of regularly spaced fibrils in the cytoplasm with no bounding structures. Although the fibers were widely spaced, other cellular complexes, such as ribosomes, were excluded from the fibril arrays. Subtomogram image averaging, made possible by the organized nature of the assemblies, uncovered the presence of an additional array of densities between the fibers. We suggest these structures constitute a self-organizing mechanism that coordinates fiber deposition and the regulation of prion inheritance.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 07 Sep 2012 10:10 |
| Last Modified: | 02 Aug 2023 16:58 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/5054 |
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