N-terminal acetylation of superoxide dismutase 1 accelerates amyloid formation without general destabilization of the apo state
(2025) In Protein Science 34(9).- Abstract
- Co- and post-translational modifications can significantly impact the structure, dynamics, and function of proteins. In this study, we investigate how N-terminal acetylation affects misfolding and self-assembly of the enzyme superoxide dismutase 1 (SOD1), implicated in amyotrophic lateral sclerosis (ALS). Studies of protein inclusions in patient samples and animal models have shown that wild-type SOD1 can form amyloid fibrils even when no mutations are found in the sod1 gene. This has identified SOD1 amyloid formation as a possible common denominator of ALS and may suggest that co- and post-translational modifications, like N-terminal acetylation found in human SOD1, can be a factor in disease development. In this work, the impact... (More)
- Co- and post-translational modifications can significantly impact the structure, dynamics, and function of proteins. In this study, we investigate how N-terminal acetylation affects misfolding and self-assembly of the enzyme superoxide dismutase 1 (SOD1), implicated in amyotrophic lateral sclerosis (ALS). Studies of protein inclusions in patient samples and animal models have shown that wild-type SOD1 can form amyloid fibrils even when no mutations are found in the sod1 gene. This has identified SOD1 amyloid formation as a possible common denominator of ALS and may suggest that co- and post-translational modifications, like N-terminal acetylation found in human SOD1, can be a factor in disease development. In this work, the impact of N-terminal acetylation of SOD1 on stability and aggregation is characterized. Results show that the structure and thermal stability of the apo state are unaffected by the modification while the amyloid formation rate is significantly enhanced. This is caused by a shortening of the nucleation phase together with an increase of fibril elongation by more than 10-fold upon N-terminal acetylation of SOD1. Collectively, the findings demonstrate how regulation by co- and post-translational modifications can influence protein misfolding and self-assembly. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/087af38f-5b6e-4192-9fdd-30ec2e7670c6
- author
- Jensen, Kristine Steen LU
- organization
- publishing date
- 2025-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid formation kinetics, amyotrophic lateral sclerosis, N-terminal acetylation, post-translational modification, superoxide dismutase 1
- in
- Protein Science
- volume
- 34
- issue
- 9
- article number
- e70267
- pages
- 13 pages
- publisher
- The Protein Society
- external identifiers
-
- pmid:40815260
- scopus:105013457643
- ISSN
- 0961-8368
- DOI
- 10.1002/pro.70267
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
- id
- 087af38f-5b6e-4192-9fdd-30ec2e7670c6
- date added to LUP
- 2025-10-09 12:20:59
- date last changed
- 2025-11-20 15:56:35
@article{087af38f-5b6e-4192-9fdd-30ec2e7670c6,
abstract = {{Co- and post-translational modifications can significantly impact the structure, dynamics, and function of proteins. In this study, we investigate how N-terminal acetylation affects misfolding and self-assembly of the enzyme superoxide dismutase 1 (SOD1), implicated in amyotrophic lateral sclerosis (ALS). Studies of protein inclusions in patient samples and animal models have shown that wild-type SOD1 can form amyloid fibrils even when no mutations are found in the <i>sod1</i> gene. This has identified SOD1 amyloid formation as a possible common denominator of ALS and may suggest that co- and post-translational modifications, like N-terminal acetylation found in human SOD1, can be a factor in disease development. In this work, the impact of N-terminal acetylation of SOD1 on stability and aggregation is characterized. Results show that the structure and thermal stability of the apo state are unaffected by the modification while the amyloid formation rate is significantly enhanced. This is caused by a shortening of the nucleation phase together with an increase of fibril elongation by more than 10-fold upon N-terminal acetylation of SOD1. Collectively, the findings demonstrate how regulation by co- and post-translational modifications can influence protein misfolding and self-assembly.}},
author = {{Jensen, Kristine Steen}},
issn = {{0961-8368}},
keywords = {{amyloid formation kinetics; amyotrophic lateral sclerosis; N-terminal acetylation; post-translational modification; superoxide dismutase 1}},
language = {{eng}},
number = {{9}},
publisher = {{The Protein Society}},
series = {{Protein Science}},
title = {{N-terminal acetylation of superoxide dismutase 1 accelerates amyloid formation without general destabilization of the apo state}},
url = {{http://dx.doi.org/10.1002/pro.70267}},
doi = {{10.1002/pro.70267}},
volume = {{34}},
year = {{2025}},
}