Formation of covalent di-tyrosine dimers in recombinant α-synuclein
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Formation of covalent di-tyrosine dimers in recombinant α-synuclein. / van Maarschalkerweerd, A; Pedersen, MN; Peterson, H; Nilsson, M; Nguyen, TTT; Skamris, T; Rand, K; Vetri, V; Langkilde, AE; Vestergaard, B.
In: Intrinsically Disordered Proteins, Vol. 3, No. 1, 19.10.2015, p. 1-12.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Formation of covalent di-tyrosine dimers in recombinant α-synuclein
AU - van Maarschalkerweerd, A
AU - Pedersen, MN
AU - Peterson, H
AU - Nilsson, M
AU - Nguyen, TTT
AU - Skamris, T
AU - Rand, K
AU - Vetri, V
AU - Langkilde, AE
AU - Vestergaard, B
N1 - doi: 10.1080/21690707.2015.1071302
PY - 2015/10/19
Y1 - 2015/10/19
N2 - Parkinson's disease is associated with fibril deposition in the diseased brain. Misfolding events of the intrinsically disordered synaptic protein α-synuclein are suggested to lead to the formation of transient oligomeric and cytotoxic species. The etiology of Parkinson's disease is further associated with mitochondrial dysfunction and formation of reactive oxygen species. Oxidative stress causes chemical modification of native α-synuclein, plausibly further influencing misfolding events. Here, we present evidence for the spontaneous formation of covalent di-tyrosine α-synuclein dimers in standard recombinant protein preparations, induced without extrinsic oxidative or nitrative agents. The dimers exhibit no secondary structure but advanced SAXS studies reveal an increased structural definition, resulting in a more hydrophobic micro-environment than the highly disordered monomer. Accordingly, monomers and dimers follow distinct fibrillation pathways.
AB - Parkinson's disease is associated with fibril deposition in the diseased brain. Misfolding events of the intrinsically disordered synaptic protein α-synuclein are suggested to lead to the formation of transient oligomeric and cytotoxic species. The etiology of Parkinson's disease is further associated with mitochondrial dysfunction and formation of reactive oxygen species. Oxidative stress causes chemical modification of native α-synuclein, plausibly further influencing misfolding events. Here, we present evidence for the spontaneous formation of covalent di-tyrosine α-synuclein dimers in standard recombinant protein preparations, induced without extrinsic oxidative or nitrative agents. The dimers exhibit no secondary structure but advanced SAXS studies reveal an increased structural definition, resulting in a more hydrophobic micro-environment than the highly disordered monomer. Accordingly, monomers and dimers follow distinct fibrillation pathways.
U2 - 10.1080/21690707.2015.1071302
DO - 10.1080/21690707.2015.1071302
M3 - Journal article
VL - 3
SP - 1
EP - 12
JO - Intrinsically Disordered Proteins
JF - Intrinsically Disordered Proteins
SN - null
IS - 1
ER -
ID: 148551955