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DIBMA nanodiscs keep α-synuclein folded

2020Journal article Open access
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authorProfile.emaildaniela.vaz@ipleiria.pt
dc.contributor.authorAdão, Regina
dc.contributor.authorCruz, Pedro F.
dc.contributor.authorVaz, Daniela C.
dc.contributor.authorFonseca, Fátima
dc.contributor.authorPedersen, Jannik Nedergaard
dc.contributor.authorFerreira-da-Silva, Frederico
dc.contributor.authorBrito, Rui M. M.
dc.contributor.authorRamos, Carlos H. I.
dc.contributor.authorOtzen, Daniel
dc.contributor.authorKeller, Sandro
dc.contributor.authorBastos, Margarida
dc.date.accessioned2020-12-16T16:25:54Z
dc.date.available2020-12-16T16:25:54Z
dc.date.issued2020
dc.description.abstractα-Synuclein (αsyn) is a cytosolic intrinsically disordered protein (IDP) known to fold into an α-helical structure when binding to membrane lipids, decreasing protein aggregation. Model membrane enable elucidation of factors critically affecting protein folding/aggregation, mostly using either small unilamellar vesicles (SUVs) or nanodiscs surrounded by membrane scaffold proteins (MSPs). Yet SUVs are mechanically strained, while MSP nanodiscs are expensive. To test the impact of lipid particle size on α-syn structuring, while overcoming the limitations associated with the lipid particles used so far, we compared the effects of large unilamellar vesicles (LUVs) and lipid-bilayer nanodiscs encapsulated by diisobutylene/maleic acid copolymer (DIBMA) on αsyn secondary-structure formation, using human-, elephant- and whale -αsyn. Our results confirm that negatively charged lipids induce αsyn folding in h-αsyn and e-αsyn but not in w-αsyn. When a mixture of zwitterionic and negatively charged lipids was used, no increase in the secondary structure was detected at 45 °C. Further, our results show that DIBMA/lipid particles (DIBMALPs) are highly suitable nanoscale membrane mimics for studying αsyn secondary-structure formation and aggregation, as folding was essentially independent of the lipid/protein ratio, in contrast with what we observed for LUVs having the same lipid compositions. This study reveals a new and promising application of polymer-encapsulated lipid-bilayer nanodiscs, due to their excellent efficiency in structuring disordered proteins such as αsyn into nontoxic α-helical structures. This will contribute to the unravelling and modelling aspects concerning protein-lipid interactions and α-helix formation by αsyn, paramount to the proposal of new methods to avoid protein aggregation and disease.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.bbamem.2020.183314pt_PT
dc.identifier.issn0005-2736
dc.identifier.urihttp://hdl.handle.net/10400.8/5233
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectAlkenespt_PT
dc.subjectHumanspt_PT
dc.subjectIntrinsically Disordered Proteinspt_PT
dc.subjectLipid Bilayerspt_PT
dc.subjectMaleatespt_PT
dc.subjectMembrane Lipidspt_PT
dc.subjectMembrane Proteinspt_PT
dc.subjectPolymerspt_PT
dc.subjectProtein Aggregatespt_PT
dc.subjectProtein Conformation, alpha-Helicalpt_PT
dc.subjectProtein Foldingpt_PT
dc.subjectProtein Structure, Secondarypt_PT
dc.subjectUnilamellar Liposomespt_PT
dc.subjectalpha-Synucleinpt_PT
dc.titleDIBMA nanodiscs keep α-synuclein foldedpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue9pt_PT
oaire.citation.startPage183314pt_PT
oaire.citation.titleBiochimica et Biophysica Acta (BBA) - Biomembranespt_PT
oaire.citation.volume1862pt_PT
person.familyNameBarroso de Moura Cipreste Vaz
person.givenNameDaniela
person.identifier.ciencia-id801A-7761-328C
person.identifier.orcid0000-0001-7562-4676
person.identifier.ridR-5243-2017
person.identifier.scopus-author-id6602838931
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication518f12af-3297-4334-b00b-c06e17b2cf27
relation.isAuthorOfPublication.latestForDiscovery518f12af-3297-4334-b00b-c06e17b2cf27

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