Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures
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...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/78008 https://orcid.org/0000-0003-1307-882X |
| _version_ | 1811076396412305408 |
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| author | Lindquist, Susan Saibil, Helen R. Seybert, Anja Habermann, Anja Winkler, Juliane Eltsov, Mikhail Perkovic, Mario Castano-Diez, Daniel |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lindquist, Susan Saibil, Helen R. Seybert, Anja Habermann, Anja Winkler, Juliane Eltsov, Mikhail Perkovic, Mario Castano-Diez, Daniel |
| author_sort | Lindquist, Susan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:21:06Z |
| format | Article |
| id | mit-1721.1/78008 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:21:06Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/780082022-09-30T20:32:16Z Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures Lindquist, Susan Saibil, Helen R. Seybert, Anja Habermann, Anja Winkler, Juliane Eltsov, Mikhail Perkovic, Mario Castano-Diez, Daniel Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Lindquist, Susan 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. 2013-03-27T21:06:24Z 2013-03-27T21:06:24Z 2012-08 2012-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/78008 Saibil, H. R. et al. “Heritable Yeast Prions Have a Highly Organized Three-dimensional Architecture with Interfiber Structures.” Proceedings of the National Academy of Sciences 109.37 (2012): 14906–14911. ©2012 National Academy of Sciences https://orcid.org/0000-0003-1307-882X en_US http://dx.doi.org/10.1073/pnas.1211976109 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Lindquist, Susan Saibil, Helen R. Seybert, Anja Habermann, Anja Winkler, Juliane Eltsov, Mikhail Perkovic, Mario Castano-Diez, Daniel Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures |
| title | Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures |
| title_full | Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures |
| title_fullStr | Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures |
| title_full_unstemmed | Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures |
| title_short | Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures |
| title_sort | heritable yeast prions have a highly organized three dimensional architecture with interfiber structures |
| url | http://hdl.handle.net/1721.1/78008 https://orcid.org/0000-0003-1307-882X |
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