Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior. / Cholak, Ersoy; Bucciarelli, Saskia; Bugge, Katrine; Johansen, Nicolai Tidemand; Vestergaard, Bente; Arleth, Lise; Kragelund, Birthe B; Langkilde, Annette E.

In: Biochemistry, Vol. 58, No. 50, 11.2019, p. 5052-5065.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Cholak, E, Bucciarelli, S, Bugge, K, Johansen, NT, Vestergaard, B, Arleth, L, Kragelund, BB & Langkilde, AE 2019, 'Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior', Biochemistry, vol. 58, no. 50, pp. 5052-5065. https://doi.org/10.1021/acs.biochem.9b00925

APA

Cholak, E., Bucciarelli, S., Bugge, K., Johansen, N. T., Vestergaard, B., Arleth, L., Kragelund, B. B., & Langkilde, A. E. (2019). Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior. Biochemistry, 58(50), 5052-5065. https://doi.org/10.1021/acs.biochem.9b00925

Vancouver

Cholak E, Bucciarelli S, Bugge K, Johansen NT, Vestergaard B, Arleth L et al. Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior. Biochemistry. 2019 Nov;58(50):5052-5065. https://doi.org/10.1021/acs.biochem.9b00925

Author

Cholak, Ersoy ; Bucciarelli, Saskia ; Bugge, Katrine ; Johansen, Nicolai Tidemand ; Vestergaard, Bente ; Arleth, Lise ; Kragelund, Birthe B ; Langkilde, Annette E. / Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior. In: Biochemistry. 2019 ; Vol. 58, No. 50. pp. 5052-5065.

Bibtex

@article{e01d1995c30544e49e32c609e651f9b8,
title = "Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior",
abstract = "A hallmark of Parkinson's disease is the presence of Lewy bodies consisting of lipids and proteins, mainly fibrillated α-synuclein (aSN). aSN is an intrinsically disordered protein exerting its physiological role in an ensemble of states, one of which coexists in large assemblies with lipids, recently termed co-structures. Here, we decipher the kinetics of aSN:lipid co-structure formation to decode its mechanism of formation, and we show that the co-structures form with a distinct stoichiometry. Through seeded fibrillation assays, we demonstrate that aSN:lipid co-structures accelerate aSN fibril nucleation compared to lipid vesicles alone. A small-angle X-ray scattering-based model is proposed in which aSN decorates the lipid vesicle surface, yielding properties similar to those of the fibril surface, enhancing fibril nucleation. The delicate balance of aSN structural states close to and on the membrane may under given conditions, e.g., increased local concentrations, be a crucial switching factor between functional and pathological behavior.",
author = "Ersoy Cholak and Saskia Bucciarelli and Katrine Bugge and Johansen, {Nicolai Tidemand} and Bente Vestergaard and Lise Arleth and Kragelund, {Birthe B} and Langkilde, {Annette E}",
year = "2019",
month = nov,
doi = "10.1021/acs.biochem.9b00925",
language = "English",
volume = "58",
pages = "5052--5065",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "50",

}

RIS

TY - JOUR

T1 - Distinct α-Synuclein:Lipid Co-Structure Complexes Affect Amyloid Nucleation through Fibril Mimetic Behavior

AU - Cholak, Ersoy

AU - Bucciarelli, Saskia

AU - Bugge, Katrine

AU - Johansen, Nicolai Tidemand

AU - Vestergaard, Bente

AU - Arleth, Lise

AU - Kragelund, Birthe B

AU - Langkilde, Annette E

PY - 2019/11

Y1 - 2019/11

N2 - A hallmark of Parkinson's disease is the presence of Lewy bodies consisting of lipids and proteins, mainly fibrillated α-synuclein (aSN). aSN is an intrinsically disordered protein exerting its physiological role in an ensemble of states, one of which coexists in large assemblies with lipids, recently termed co-structures. Here, we decipher the kinetics of aSN:lipid co-structure formation to decode its mechanism of formation, and we show that the co-structures form with a distinct stoichiometry. Through seeded fibrillation assays, we demonstrate that aSN:lipid co-structures accelerate aSN fibril nucleation compared to lipid vesicles alone. A small-angle X-ray scattering-based model is proposed in which aSN decorates the lipid vesicle surface, yielding properties similar to those of the fibril surface, enhancing fibril nucleation. The delicate balance of aSN structural states close to and on the membrane may under given conditions, e.g., increased local concentrations, be a crucial switching factor between functional and pathological behavior.

AB - A hallmark of Parkinson's disease is the presence of Lewy bodies consisting of lipids and proteins, mainly fibrillated α-synuclein (aSN). aSN is an intrinsically disordered protein exerting its physiological role in an ensemble of states, one of which coexists in large assemblies with lipids, recently termed co-structures. Here, we decipher the kinetics of aSN:lipid co-structure formation to decode its mechanism of formation, and we show that the co-structures form with a distinct stoichiometry. Through seeded fibrillation assays, we demonstrate that aSN:lipid co-structures accelerate aSN fibril nucleation compared to lipid vesicles alone. A small-angle X-ray scattering-based model is proposed in which aSN decorates the lipid vesicle surface, yielding properties similar to those of the fibril surface, enhancing fibril nucleation. The delicate balance of aSN structural states close to and on the membrane may under given conditions, e.g., increased local concentrations, be a crucial switching factor between functional and pathological behavior.

U2 - 10.1021/acs.biochem.9b00925

DO - 10.1021/acs.biochem.9b00925

M3 - Journal article

C2 - 31747254

VL - 58

SP - 5052

EP - 5065

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 50

ER -

ID: 231303378