Adsorption of unfolded Cu/Zn superoxide dismutase onto hydrophobic surfaces catalyzes its formation of amyloid fibrils
Khan, Ashhar LU ; Weininger, Ulrich LU ; Kjellström, Sven LU ; Deep, Shashank and Akke, Mikael LU
(2019)
In Protein Engineering Design & Selection
32(2).
p.77-85
- Abstract
- Intracellular aggregates of superoxide dismutase 1 (SOD1) are associated with amyotrophic lateral sclerosis. In vivo, aggregation occurs in a complex and dense molecular environment with chemically heterogeneous surfaces. To investigate how SOD1 fibril formation is affected by surfaces, we used an in vitro model system enabling us to vary the molecular features of both SOD1 and the surfaces, as well as the surface area. We compared fibril formation in hydrophilic and hydrophobic sample wells, as a function of denaturant concentration and extraneous hydrophobic surface area. In the presence of hydrophobic surfaces, SOD1 unfolding promotes fibril nucleation. By contrast, in the presence of hydrophilic surfaces, increasing denaturant... (More)
- Intracellular aggregates of superoxide dismutase 1 (SOD1) are associated with amyotrophic lateral sclerosis. In vivo, aggregation occurs in a complex and dense molecular environment with chemically heterogeneous surfaces. To investigate how SOD1 fibril formation is affected by surfaces, we used an in vitro model system enabling us to vary the molecular features of both SOD1 and the surfaces, as well as the surface area. We compared fibril formation in hydrophilic and hydrophobic sample wells, as a function of denaturant concentration and extraneous hydrophobic surface area. In the presence of hydrophobic surfaces, SOD1 unfolding promotes fibril nucleation. By contrast, in the presence of hydrophilic surfaces, increasing denaturant concentration retards the onset of fibril formation. We conclude that the mechanism of fibril formation depends on the surrounding surfaces and that the nucleating species might correspond to different conformational states of SOD1 depending on the nature of these surfaces. (Less)
- Abstract (Swedish)
- Intracellular aggregates of superoxide dismutase 1 (SOD1) are associated with amyotrophic lateral sclerosis. In vivo, aggregation occurs in a complex and dense molecular environment with chemically heterogeneous surfaces. To investigate how SOD1 fibril formation is affected by surfaces, we used an in vitro model system enabling us to vary the molecular features of both SOD1 and the surfaces, as well as the surface area. We compared fibril formation in hydrophilic and hydrophobic sample wells, as a function of denaturant concentration and extraneous hydrophobic surface area. In the presence of hydrophobic surfaces, SOD1 unfolding promotes fibril nucleation. By contrast, in the presence of hydrophilic surfaces, increasing denaturant... (More)
- Intracellular aggregates of superoxide dismutase 1 (SOD1) are associated with amyotrophic lateral sclerosis. In vivo, aggregation occurs in a complex and dense molecular environment with chemically heterogeneous surfaces. To investigate how SOD1 fibril formation is affected by surfaces, we used an in vitro model system enabling us to vary the molecular features of both SOD1 and the surfaces, as well as the surface area. We compared fibril formation in hydrophilic and hydrophobic sample wells, as a function of denaturant concentration and extraneous hydrophobic surface area. In the presence of hydrophobic surfaces, SOD1 unfolding promotes fibril nucleation. By contrast, in the presence of hydrophilic surfaces, increasing denaturant concentration retards the onset of fibril formation. We conclude that the mechanism of fibril formation depends on the surrounding surfaces and that the nucleating species might correspond to different conformational states of SOD1 depending on the nature of these surfaces. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/790e852b-bafd-494d-be62-caa6a8013aab
- author
- Khan, Ashhar
LU
; Weininger, Ulrich
LU
; Kjellström, Sven
LU
; Deep, Shashank
and Akke, Mikael
LU
- organization
- publishing date
- 2019-09-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Protein Engineering Design & Selection
- volume
- 32
- issue
- 2
- pages
- 77 - 85
- publisher
- Oxford University Press
- external identifiers
-
- pmid:31832682
- scopus:85076403259
- ISSN
- 1741-0126
- DOI
- 10.1093/protein/gzz033
- language
- English
- LU publication?
- yes
- id
- 790e852b-bafd-494d-be62-caa6a8013aab
- date added to LUP
- 2019-09-10 18:39:04
- date last changed
- 2022-03-18 04:24:35
@article{790e852b-bafd-494d-be62-caa6a8013aab,
abstract = {{Intracellular aggregates of superoxide dismutase 1 (SOD1) are associated with amyotrophic lateral sclerosis. In vivo, aggregation occurs in a complex and dense molecular environment with chemically heterogeneous surfaces. To investigate how SOD1 fibril formation is affected by surfaces, we used an in vitro model system enabling us to vary the molecular features of both SOD1 and the surfaces, as well as the surface area. We compared fibril formation in hydrophilic and hydrophobic sample wells, as a function of denaturant concentration and extraneous hydrophobic surface area. In the presence of hydrophobic surfaces, SOD1 unfolding promotes fibril nucleation. By contrast, in the presence of hydrophilic surfaces, increasing denaturant concentration retards the onset of fibril formation. We conclude that the mechanism of fibril formation depends on the surrounding surfaces and that the nucleating species might correspond to different conformational states of SOD1 depending on the nature of these surfaces.}},
author = {{Khan, Ashhar and Weininger, Ulrich and Kjellström, Sven and Deep, Shashank and Akke, Mikael}},
issn = {{1741-0126}},
language = {{eng}},
month = {{09}},
number = {{2}},
pages = {{77--85}},
publisher = {{Oxford University Press}},
series = {{Protein Engineering Design & Selection}},
title = {{Adsorption of unfolded Cu/Zn superoxide dismutase onto hydrophobic surfaces catalyzes its formation of amyloid fibrils}},
url = {{https://lup.lub.lu.se/search/files/69322378/Khan_surface_190719.pdf}},
doi = {{10.1093/protein/gzz033}},
volume = {{32}},
year = {{2019}},
}