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Residue-specific bi...
Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides
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- Berntsson, Elina (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden; Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia
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- Vosough, Faraz (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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- Svantesson, Teodor (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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- Pansieri, Jonathan (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Iashchishyn, Igor (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Ostojic, Lucija (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Dong, Xiaolin (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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- Paul, Suman (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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- Jarvet, Jüri (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden; National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
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- Roos, Per M. (author)
- Karolinska Institutet
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- Barth, Andreas (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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- Morozova-Roche, Ludmilla (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Gräslund, Astrid (author)
- Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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- Wärmländer, Sebastian K T S (author)
- Chemistry Section, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden
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(creator_code:org_t)
- 2023-02-27
- 2023
- English.
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Abstract
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- Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD brains display deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-β (Aβ) peptides, and Aβ oligomers are likely a toxic species in AD pathology. AD patients display altered metal homeostasis, and AD plaques show elevated concentrations of metals such as Cu, Fe, and Zn. Yet, the metal chemistry in AD pathology remains unclear. Ni(II) ions are known to interact with Aβ peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods-mainly spectroscopy and imaging techniques-to characterize Aβ/Ni(II) interactions in vitro, for different Aβ variants: Aβ(1-40), Aβ(1-40)(H6A, H13A, H14A), Aβ(4-40), and Aβ(1-42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length Aβ monomers. Equimolar amounts of Ni(II) ions retard Aβ aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)·Aβ binding affinity is in the low µM range. The redox-active Ni(II) ions induce formation of dityrosine cross-links via redox chemistry, thereby creating covalent Aβ dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in Aβ monomers, while in a membrane-mimicking environment (SDS micelles) coil-coil helix interactions appear to be induced. For SDS-stabilized Aβ oligomers, Ni(II) ions direct the oligomers towards larger sizes and more diverse (heterogeneous) populations. All of these structural rearrangements may be relevant for the Aβ aggregation processes that are involved in AD brain pathology.
Subject headings
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Berntsson, Elina
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Vosough, Faraz
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Svantesson, Teod ...
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Pansieri, Jonath ...
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Iashchishyn, Igo ...
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Ostojic, Lucija
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Dong, Xiaolin
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Paul, Suman
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Jarvet, Jüri
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Roos, Per M.
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Barth, Andreas
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Morozova-Roche, ...
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Gräslund, Astrid
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Wärmländer, Seba ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Structural Biolo ...
- Articles in the publication
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Scientific Repor ...
- By the university
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Umeå University
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Karolinska Institutet