Adsorption of unfolded Cu/Zn superoxide dismutase onto hydrophobic surfaces catalyzes its formation of amyloid fibrils. Issue 2 (6th September 2019)

• Record Type: Journal Article
• Authors: Khan, Mohammad Ashhar I; Weininger, Ulrich; Kjellström, Sven; Deep, Shashank; Akke, Mikael
• Editors: Valerie, Daggett
• Is Part Of: Protein engineering, design & selection. Volume 32:Issue 2(2019)
• Page Start: 77
• Page End: 85
• Publication Date: 2019-09-06
• Subjects: amyotrophic lateral sclerosis -- protein aggregation -- protein unfolding -- protein unfolding -- surface adsorption -- surface catalyzed nucleation; Protein engineering -- Periodicals; 660.63
• DOI: 10.1093/protein/gzz033
• Languages: English
• ISSNs: 1741-0126

Abstract

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.