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A beta(1-42) tetram...
A beta(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage
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Ciudad, S. (author)
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Puig, E. (author)
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Botzanowski, T. (author)
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Meigooni, M. (author)
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Arango, A. S. (author)
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Do, J. (author)
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- Mayzel, Maxim (author)
- Gothenburg University,Göteborgs universitet,Svenskt NMR-centrum vid Göteborgs universitet,Swedish NMR Centre at Göteborg University
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Bayoumi, M. (author)
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Chaignepain, S. (author)
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Maglia, G. (author)
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Cianferani, S. (author)
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- Orekhov, Vladislav, 1966 (author)
- Gothenburg University,Göteborgs universitet,Svenskt NMR-centrum vid Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Swedish NMR Centre at Göteborg University,Department of Chemistry and Molecular Biology
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Tajkhorshid, E. (author)
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Bardiaux, B. (author)
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Carulla, N. (author)
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(creator_code:org_t)
- 2020-06-15
- 2020
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Abstract
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- Formation of amyloid-beta (A beta) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimers disease (AD). Here, we present the three-dimensional structure of an A beta oligomer formed in a membrane mimicking environment, namely an A beta(1-42) tetramer, which comprises a six stranded beta-sheet core. The two faces of the beta-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of A beta(1-42) in the sample, A beta(1-42) octamers are also formed, made by two A beta(1-42) tetramers facing each other forming a beta-sandwich structure. Notably, A beta(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core beta-sheets edges of the oligomers.
Subject headings
- NATURVETENSKAP -- Matematik (hsv//swe)
- NATURAL SCIENCES -- Mathematics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ciudad, S.
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Puig, E.
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Botzanowski, T.
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Meigooni, M.
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Arango, A. S.
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Do, J.
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show more...
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Mayzel, Maxim
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Bayoumi, M.
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Chaignepain, S.
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Maglia, G.
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Cianferani, S.
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Orekhov, Vladisl ...
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Tajkhorshid, E.
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Bardiaux, B.
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Carulla, N.
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Mathematics
- Articles in the publication
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Nature Communica ...
- By the university
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University of Gothenburg