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Journal articles
Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage
Sonia Ciudad
1, 2
Eduard Puig
1, 2
Thomas Botzanowski
3
Moeen Meigooni
4
Andres Arango
4
Jimmy Do
4
Maxim Mayzel
5
Mariam Bayoumi
6
Stéphane Chaignepain
1
Giovanni Maglia
7
Sarah Cianférani
8
Vladislav Orekhov
5
Emad Tajkhorshid
4
Benjamin Bardiaux
9, 10
Natàlia Carulla
11, 1
8
LSMBO - Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg]
DSA-IPHC - Sciences Analytiques et Interactions Ioniques et Biomoléculaires
Sonia Ciudad 1, 2
Author
Eduard Puig 1, 2
Author
Thomas Botzanowski 3
Author
Moeen Meigooni 4
Author
Stéphane Chaignepain 1
Author
Giovanni Maglia 7
Author
Sarah Cianférani 8
Author
Vladislav Orekhov 5
Author
1
CBMN - Chimie et Biologie des Membranes et des Nanoobjets (IECB 2, rue Robert Escarpit 33607 PESSAC CEDEX - France)
- Université Sciences et Technologies - Bordeaux 1 (351 cours de la Libération - 33405 Talence cedex - France)
- ENITAB - École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (France)
- CNRS - Centre National de la Recherche Scientifique : UMR5248 (France)
2
IRB - Institute for Research in Biomedicine [Barcelona, Spain] (Parc Científic de Barcelona C/ Baldiri Reixac 10 08028 Barcelona - Spain)
- University of Barcelona (Gran Via de les Corts Catalanes, 585, 08007 Barcelona - Spain)
3
IPHC - Institut Pluridisciplinaire Hubert Curien (23 rue Loess - BP 28 67037 Strasbourg Cedex - France)
- UNISTRA - Université de Strasbourg (4 rue Blaise Pascal - CS 90032 - 67081 Strasbourg cedex - France)
- IN2P3 - Institut National de Physique Nucléaire et de Physique des Particules du CNRS (France)
- CNRS - Centre National de la Recherche Scientifique : UMR7178 (France)
4
University of Illinois at Urbana-Champaign [Urbana] (205 N. Mathews Ave., Urbana-Champaign, IL 61801 - United States)
- University of Illinois System (108 Henry Administration Bldg. Urbana, IL 61801 - United States)
5
GU - University of Gothenburg (Box 100, SE-405 30 Gothenburg - Sweden)
6
KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven (Oude Markt 13 - bus 5005, 3000 Leuven - Belgium)
7
University of Groningen [Groningen] (PO Box 72 , 9700 AB Groningen - Netherlands)
8
LSMBO - Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (23 rue du loess - BP28,
67037 Strasbourg cedex 2 - France)
- DSA-IPHC - Sciences Analytiques et Interactions Ioniques et Biomoléculaires (25, rue Becquerel 67087 Strasbourg Cedex 2 - France)
- IPHC - Institut Pluridisciplinaire Hubert Curien (23 rue Loess - BP 28 67037 Strasbourg Cedex - France)
- UNISTRA - Université de Strasbourg (4 rue Blaise Pascal - CS 90032 - 67081 Strasbourg cedex - France)
- IN2P3 - Institut National de Physique Nucléaire et de Physique des Particules du CNRS (France)
- CNRS - Centre National de la Recherche Scientifique : UMR7178 (France)
- IPHC - Institut Pluridisciplinaire Hubert Curien (23 rue Loess - BP 28 67037 Strasbourg Cedex - France)
9
Bioinformatique structurale (Département de Biologie structurale et Chimie, 25-28, rue du Docteur Roux - 75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR3528 (France)
10
C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative (25-28 rue du docteur Roux, 75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : USR3756 (France)
11
IRB - Institute for Research in Biomedicine (IRB Barcelona) (Baldiri Reixac, 10, E-08028 Barcelona, Spain - Spain)
Abstract : Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer's disease (AD). Here, we present the three-dimensional structure of an Aβ oligomer formed in a membrane mimicking environment, namely an Aβ(1-42) tetramer, which comprises a six stranded β-sheet core. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of Aβ(1-42) in the sample, Aβ(1-42) octamers are also formed, made by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. Notably, Aβ(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 β-sheets edges of the oligomers.
Document type :
Journal articles
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02874153
Contributor : Benjamin Bardiaux <>
Submitted on : Thursday, June 18, 2020 - 6:34:24 PM
Last modification on : Saturday, June 20, 2020 - 3:34:02 AM
Contributor : Benjamin Bardiaux <>
Submitted on : Thursday, June 18, 2020 - 6:34:24 PM
Last modification on : Saturday, June 20, 2020 - 3:34:02 AM
Licence
Distributed under a Creative Commons Attribution 4.0 International License
Identifiers
- HAL Id : pasteur-02874153, version 1
- DOI : 10.1038/s41467-020-16566-1
- PUBMED : 32541820
Citation
Sonia Ciudad, Eduard Puig, Thomas Botzanowski, Moeen Meigooni, Andres Arango, et al.. Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.3014. ⟨10.1038/s41467-020-16566-1⟩. ⟨pasteur-02874153⟩
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