Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/182271
Title: | Threonine-rich carboxyl-terminal extension drives aggregation of stalled polypeptides | Authors: | Chang, Denyse Weili Yoon, Mi-Jeong Yeo, Kian Hua Choe, Young-Jun |
Keywords: | Medicine, Health and Life Sciences | Issue Date: | 2024 | Source: | Chang, D. W., Yoon, M., Yeo, K. H. & Choe, Y. (2024). Threonine-rich carboxyl-terminal extension drives aggregation of stalled polypeptides. Molecular Cell, 84(22), 4334-4349.e7. https://dx.doi.org/10.1016/j.molcel.2024.10.011 | Project: | NAP SUG RG28/22 |
Journal: | Molecular Cell | Abstract: | Ribosomes translating damaged mRNAs may stall and prematurely split into their large and small subunits. The split large ribosome subunits can continue elongating stalled polypeptides. In yeast, this mRNA-independent translation appends the C-terminal alanine/threonine tail (CAT tail) to stalled polypeptides. If not degraded by the ribosome-associated quality control (RQC), CAT-tailed stalled polypeptides form aggregates. How the CAT tail, a low-complexity region composed of alanine and threonine, drives protein aggregation remains unknown. In this study, we demonstrate that C-terminal polythreonine or threonine-enriched tails form detergent-resistant aggregates. These aggregates exhibit a robust seeding effect on shorter tails with lower threonine content, elucidating how heterogeneous CAT tails co-aggregate. Polythreonine aggregates sequester molecular chaperones, disturbing proteostasis and provoking the heat shock response. Furthermore, polythreonine cross-seeds detergent-resistant polyserine aggregation, indicating structural similarity between the two aggregates. This study identifies polythreonine and polyserine as a distinct group of aggregation-prone protein motifs. | URI: | https://hdl.handle.net/10356/182271 | ISSN: | 1097-2765 | DOI: | 10.1016/j.molcel.2024.10.011 | Schools: | School of Biological Sciences | Rights: | © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
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1-s2.0-S1097276524008347-main.pdf | 6.59 MB | Adobe PDF | ![]() View/Open |
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