Formation of covalent di-tyrosine dimers in recombinant α-synuclein

Valeria Vetri, Rand, Nilsson, Bente Vestergaard, Nguyen, Pedersen, Andreas Van Maarschalkerweerd, Skamris, Pedersen, Martin Nors Pedersen, Peterson, Nilsson, Annette Eva Langkilde

Risultato della ricerca: Articlepeer review

9 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1-12
Numero di pagine12
RivistaIntrinsically Disordered Proteins
Volume3
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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