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Daniel Otzen

DIBMA nanodiscs keep α-synuclein folded

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Standard

DIBMA nanodiscs keep α-synuclein folded. / Adão, Regina; Cruz, Pedro F; Vaz, Daniela C et al.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1862, No. 9, 183314, 09.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Adão, R, Cruz, PF, Vaz, DC, Fonseca, F, Pedersen, JN, Ferreira-da-Silva, F, Brito, RMM, Ramos, CHI, Otzen, D, Keller, S & Bastos, M 2020, 'DIBMA nanodiscs keep α-synuclein folded', Biochimica et Biophysica Acta - Biomembranes, vol. 1862, no. 9, 183314. https://doi.org/10.1016/j.bbamem.2020.183314

APA

Adão, R., Cruz, P. F., Vaz, D. C., Fonseca, F., Pedersen, J. N., Ferreira-da-Silva, F., Brito, R. M. M., Ramos, C. H. I., Otzen, D., Keller, S., & Bastos, M. (2020). DIBMA nanodiscs keep α-synuclein folded. Biochimica et Biophysica Acta - Biomembranes, 1862(9), [183314]. https://doi.org/10.1016/j.bbamem.2020.183314

CBE

Adão R, Cruz PF, Vaz DC, Fonseca F, Pedersen JN, Ferreira-da-Silva F, Brito RMM, Ramos CHI, Otzen D, Keller S, et al. 2020. DIBMA nanodiscs keep α-synuclein folded. Biochimica et Biophysica Acta - Biomembranes. 1862(9):Article 183314. https://doi.org/10.1016/j.bbamem.2020.183314

MLA

Adão, Regina et al. "DIBMA nanodiscs keep α-synuclein folded". Biochimica et Biophysica Acta - Biomembranes. 2020. 1862(9). https://doi.org/10.1016/j.bbamem.2020.183314

Vancouver

Adão R, Cruz PF, Vaz DC, Fonseca F, Pedersen JN, Ferreira-da-Silva F et al. DIBMA nanodiscs keep α-synuclein folded. Biochimica et Biophysica Acta - Biomembranes. 2020 Sep;1862(9):183314. doi: 10.1016/j.bbamem.2020.183314

Author

Adão, Regina ; Cruz, Pedro F ; Vaz, Daniela C et al. / DIBMA nanodiscs keep α-synuclein folded. In: Biochimica et Biophysica Acta - Biomembranes. 2020 ; Vol. 1862, No. 9.

Bibtex

@article{2afddd29c6a14d3da835de06bec32a84,
title = "DIBMA nanodiscs keep α-synuclein folded",
abstract = "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.",
keywords = "DIBMA, DIBMALPs, Lipid nanodiscs, Membrane lipids, Secondary structure, α-Synuclein",
author = "Regina Ad{\~a}o and Cruz, {Pedro F} and Vaz, {Daniela C} and F{\'a}tima Fonseca and Pedersen, {Jannik Nedergaard} and Frederico Ferreira-da-Silva and Brito, {Rui M M} and Ramos, {Carlos H I} and Daniel Otzen and Sandro Keller and Margarida Bastos",
note = "Copyright {\textcopyright} 2020 Elsevier B.V. All rights reserved.",
year = "2020",
month = sep,
doi = "10.1016/j.bbamem.2020.183314",
language = "English",
volume = "1862",
journal = "B B A - Biomembranes",
issn = "0005-2736",
publisher = "Elsevier BV",
number = "9",

}

RIS

TY - JOUR

T1 - DIBMA nanodiscs keep α-synuclein folded

AU - Adão, Regina

AU - Cruz, Pedro F

AU - Vaz, Daniela C

AU - Fonseca, Fátima

AU - Pedersen, Jannik Nedergaard

AU - Ferreira-da-Silva, Frederico

AU - Brito, Rui M M

AU - Ramos, Carlos H I

AU - Otzen, Daniel

AU - Keller, Sandro

AU - Bastos, Margarida

N1 - Copyright © 2020 Elsevier B.V. All rights reserved.

PY - 2020/9

Y1 - 2020/9

N2 - 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.

AB - 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.

KW - DIBMA

KW - DIBMALPs

KW - Lipid nanodiscs

KW - Membrane lipids

KW - Secondary structure

KW - α-Synuclein

U2 - 10.1016/j.bbamem.2020.183314

DO - 10.1016/j.bbamem.2020.183314

M3 - Journal article

C2 - 32304757

VL - 1862

JO - B B A - Biomembranes

JF - B B A - Biomembranes

SN - 0005-2736

IS - 9

M1 - 183314

ER -