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MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions

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

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MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions. / Yoshimura, Yuichi; Holmberg, Mats; Kukic, Predrag et al.

In: Journal of Biological Chemistry, Vol. 292, No. 20, 2017, p. 8269-8278.

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

Harvard

Yoshimura, Y, Holmberg, M, Kukic, P, Andersen, CB, Mata-Cabana, A, Falsone, SF, Vendruscolo, M, Nollen, EAA & Mulder, F 2017, 'MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions', Journal of Biological Chemistry, vol. 292, no. 20, pp. 8269-8278. https://doi.org/10.1074/jbc.M116.764886

APA

Yoshimura, Y., Holmberg, M., Kukic, P., Andersen, C. B., Mata-Cabana, A., Falsone, S. F., Vendruscolo, M., Nollen, E. A. A., & Mulder, F. (2017). MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions. Journal of Biological Chemistry, 292(20), 8269-8278. https://doi.org/10.1074/jbc.M116.764886

CBE

Yoshimura Y, Holmberg M, Kukic P, Andersen CB, Mata-Cabana A, Falsone SF, Vendruscolo M, Nollen EAA, Mulder F. 2017. MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions. Journal of Biological Chemistry. 292(20):8269-8278. https://doi.org/10.1074/jbc.M116.764886

MLA

Vancouver

Yoshimura Y, Holmberg M, Kukic P, Andersen CB, Mata-Cabana A, Falsone SF et al. MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions. Journal of Biological Chemistry. 2017;292(20):8269-8278. doi: 10.1074/jbc.M116.764886

Author

Yoshimura, Yuichi ; Holmberg, Mats ; Kukic, Predrag et al. / MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 20. pp. 8269-8278.

Bibtex

@article{92fedc5865d0480481700645c09e9c1f,
title = "MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions",
abstract = "Aberrant protein aggregation underlies a variety of age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Little is known, however, about the molecular mechanisms that modulate the aggregation process in the cellular environment. Recently, MOAG-4/SERF has been identified as a class of evolutionarily conserved proteins that positively regulates aggregate formation. Here, by using nuclear magnetic resonance (NMR) spectroscopy, we examine the mechanism of action of MOAG-4 by characterizing its interaction with α-synuclein (α-Syn). NMR chemical shift perturbations demonstrate that a positively charged segment of MOAG-4 forms a transiently populated α-helix that interacts with the negatively charged C terminus of α-Syn. This process interferes with the intramolecular interactions between the N- and C-terminal regions of α-Syn, resulting in the protein populating less compact forms and aggregating more readily. These results provide a compelling example of the complex competition between molecular and cellular factors that protect against protein aggregation and those that promote it.",
keywords = "Journal Article",
author = "Yuichi Yoshimura and Mats Holmberg and Predrag Kukic and Andersen, {Camilla Bertel} and Alejandro Mata-Cabana and Falsone, {S. Fabio} and Michele Vendruscolo and Nollen, {Ellen A.A.} and Frans Mulder",
note = "{\textcopyright} 2017 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2017",
doi = "10.1074/jbc.M116.764886",
language = "English",
volume = "292",
pages = "8269--8278",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "20",

}

RIS

TY - JOUR

T1 - MOAG-4 promotes the aggregation of α-synuclein by competing with self-protective electrostatic interactions

AU - Yoshimura, Yuichi

AU - Holmberg, Mats

AU - Kukic, Predrag

AU - Andersen, Camilla Bertel

AU - Mata-Cabana, Alejandro

AU - Falsone, S. Fabio

AU - Vendruscolo, Michele

AU - Nollen, Ellen A.A.

AU - Mulder, Frans

N1 - © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2017

Y1 - 2017

N2 - Aberrant protein aggregation underlies a variety of age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Little is known, however, about the molecular mechanisms that modulate the aggregation process in the cellular environment. Recently, MOAG-4/SERF has been identified as a class of evolutionarily conserved proteins that positively regulates aggregate formation. Here, by using nuclear magnetic resonance (NMR) spectroscopy, we examine the mechanism of action of MOAG-4 by characterizing its interaction with α-synuclein (α-Syn). NMR chemical shift perturbations demonstrate that a positively charged segment of MOAG-4 forms a transiently populated α-helix that interacts with the negatively charged C terminus of α-Syn. This process interferes with the intramolecular interactions between the N- and C-terminal regions of α-Syn, resulting in the protein populating less compact forms and aggregating more readily. These results provide a compelling example of the complex competition between molecular and cellular factors that protect against protein aggregation and those that promote it.

AB - Aberrant protein aggregation underlies a variety of age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Little is known, however, about the molecular mechanisms that modulate the aggregation process in the cellular environment. Recently, MOAG-4/SERF has been identified as a class of evolutionarily conserved proteins that positively regulates aggregate formation. Here, by using nuclear magnetic resonance (NMR) spectroscopy, we examine the mechanism of action of MOAG-4 by characterizing its interaction with α-synuclein (α-Syn). NMR chemical shift perturbations demonstrate that a positively charged segment of MOAG-4 forms a transiently populated α-helix that interacts with the negatively charged C terminus of α-Syn. This process interferes with the intramolecular interactions between the N- and C-terminal regions of α-Syn, resulting in the protein populating less compact forms and aggregating more readily. These results provide a compelling example of the complex competition between molecular and cellular factors that protect against protein aggregation and those that promote it.

KW - Journal Article

U2 - 10.1074/jbc.M116.764886

DO - 10.1074/jbc.M116.764886

M3 - Journal article

C2 - 28336532

VL - 292

SP - 8269

EP - 8278

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 20

ER -