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

A van Maarschalkerweerd, MN Pedersen, H Peterson, M Nilsson, TTT Nguyen, T Skamris, K Rand, V Vetri, AE Langkilde, B Vestergaard

Research output: Contribution to journalJournal articleResearchpeer-review

15 Citations (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.
Original languageEnglish
JournalIntrinsically Disordered Proteins
Volume3
Issue number1
Pages (from-to)1-12
Number of pages12
ISSNnull
DOIs
Publication statusPublished - 19 Oct 2015

Bibliographical note

doi: 10.1080/21690707.2015.1071302

Cite this