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Stabilization of a Membrane-Associated Amyloid-beta Oligomer for Its Validation in Alzheimer's Disease

dc.rights.licenseopenen_US
dc.contributor.authorSERRA-BATISTE, Montserrat
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorTOLCHARD, James
dc.contributor.authorGIUSTI, Fabrice
dc.contributor.authorZOONENS, Manuela
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorCARULLA, Natalia
dc.date.accessioned2020-04-08T09:19:50Z
dc.date.available2020-04-08T09:19:50Z
dc.date.issued2018
dc.identifier.issn2296-889Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/4162
dc.description.abstractEnWe have recently reported on the preparation of a membrane-associated beta-barrel Pore-Forming Abeta42 Oligomer (betaPFOAbeta42). It corresponds to a stable and homogeneous Abeta42 oligomer that inserts into lipid bilayers as a well-defined pore and adopts a specific structure with characteristics of a beta-barrel arrangement. As a follow-up of this work, we aim to establish betaPFOAbeta42's relevance in Alzheimer's disease (AD). However, betaPFOAbeta42 is formed under dodecyl phosphocholine (DPC) micelle conditions-intended to mimic the hydrophobic environment of membranes-which are dynamic. Consequently, dilution of the betaPFOAbeta42/DPC complex in a detergent-free buffer leads to dispersion of the DPC molecules from the oligomer surface, leaving the oligomer without the hydrophobic micelle belt that stabilizes it. Since dilution is required for any biological test, transfer of betaPFOAbeta42 from DPC micelles into another hydrophobic biomimetic membrane environment, that remains associated with betaPFOAbeta42 even under high dilution conditions, is a requisite for the validation of betaPFOAbeta42 in AD. Here we describe conditions for exchanging DPC micelles with amphipols (APols), which are amphipathic polymers designed to stabilize membrane proteins in aqueous solutions. APols bind in an irreversible but non-covalent manner to the hydrophobic surface of membrane proteins preserving their structure even under extreme dilution conditions. We tested three types of APols with distinct physical-chemical properties and found that the betaPFOAbeta42/DPC complex can only be trapped in non-ionic APols (NAPols). The characterization of the resulting betaPFOAbeta42/NAPol complex by biochemical tools and structural biology techniques allowed us to establish that the oligomer structure is maintained even under high dilution. Based on these findings, this work constitutes a first step towards the in vivo validation of betaPFOAbeta42 in AD.
dc.language.isoENen_US
dc.title.enStabilization of a Membrane-Associated Amyloid-beta Oligomer for Its Validation in Alzheimer's Disease
dc.title.alternativeFront. Mol. Biosci.en_US
dc.typeArticle de revueen_US
dc.identifier.doi10.3389/fmolb.2018.00038
dc.subject.halChimie/Matériauxen_US
bordeaux.journalFrontiers in molecular biosciencesen_US
bordeaux.page38-38en_US
bordeaux.volume5en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03160504
hal.version1
hal.date.transferred2021-03-05T10:44:55Z
hal.exporttrue
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