Widespread capacity for conformational memory in the human proteome
Abstract/Contents
- Abstract
- Biomolecular condensation is a fundamental principle of cellular organization. In extreme cases, this collective behavior can store and transmit information, driving cellular memory with prion-like qualities. Although multiple examples have been identified in microbes, this behavior is assumed to be rare in metazoans. By coupling changes in protein stability to cellular fitness, we generated a quantitative atlas of self-assembly across the human proteome. Spanning multiple orders of magnitude, these measurements reveal that at least one-quarter of human proteins have the capacity to self-assemble; nearly three-quarters of these can persist over many cell divisions. This conformational memory was strongly enriched among proteins involved in key developmental decisions, stress responses, and aging. When purified in vitro these proteins formed assemblies that could autonomously replicate. Yet most did not form amyloid and were not overtly toxic. Moreover, the protein domains necessary for these behaviors often did not resemble those in classical prions. Examining a large library of human genetic variants, we find that disease-associated mutations commonly perturb conformational memory. Our results suggest that the capacity to store and transmit information is ubiquitous in the human proteome and that its dysfunction is a central feature of aging and disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lozanoski, Thomas Michael |
|---|---|
| Degree supervisor | Jarosz, Daniel |
| Thesis advisor | Jarosz, Daniel |
| Thesis advisor | Fischbach, Michael |
| Thesis advisor | Wysocka, Joanna, Ph. D |
| Degree committee member | Fischbach, Michael |
| Degree committee member | Wysocka, Joanna, Ph. D |
| Associated with | Stanford University, School of Engineering |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Thomas Michael Lozanoski. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/wx309rq3304 |
Access conditions
- Copyright
- © 2023 by Thomas Michael Lozanoski
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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