Aarhus Universitets segl

English

Du er her: AU » Om AU » Organisation » DIBMA nanodiscs keep α-synuclein folded

Om AU

DIBMA nanodiscs keep α-synuclein folded

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

DOI

  • Regina Adão, University of Porto
    • ,
  • Pedro F Cruz, University of Coimbra
    • ,
  • Daniela C Vaz, University of Coimbra, Polytechnic Institute of Leiria
    • ,
  • Fátima Fonseca, i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto
    • ,
  • Jannik Nedergaard Pedersen
    • ,
  • Frederico Ferreira-da-Silva, i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto
    • ,
  • Rui M M Brito, University of Coimbra
    • ,
  • Carlos H I Ramos, Institute of Chemistry, University of Campinas-UNICAMP, Brazil.
    • ,
  • Daniel Otzen
  • Sandro Keller, Molecular Biophysics, Technische Universität Kaiserslautern (TUK), Germany.
    • ,
  • Margarida Bastos, University of Porto

α-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.

OriginalsprogEngelsk
Artikelnummer183314
TidsskriftBiochimica et Biophysica Acta - Biomembranes
Vol/bind1862
Nummer9
Antal sider16
ISSN0005-2736
DOI
StatusUdgivet - sep. 2020

Se relationer på Aarhus Universitet Citationsformater

ID: 184904293