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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