Alpha-synuclein has an altered conformation and shows a tight intermolecular interaction with ubiquitin in Lewy bodies

N. Sharma, P. J. McLean, H. Kawamata, M. C. Irizarry, B. T. Hyman

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

α-Synuclein, a protein in which two mutations have been identified that cause autosomal dominant Parkinson's disease, is thought to serve as a nidus for the development of a Lewy body. We hypothesized that α-synuclein would display different intra- and intermolecular associations in Lewy bodies than it does in its normal intracellular compartments. Using sensitive fluorescence resonance energy transfer (FRET) techniques, we found evidence that α-synuclein is more compact and in closer association with other α-synuclein molecules in Lewy bodies than it is in the neuropil. In addition, we found evidence of a close, direct intermolecular interaction between the N terminus of α-synuclein and ubiquitin. These observations provide support for the hypothesis that in Lewy bodies α-synuclein adopts an altered three-dimensional structure and undergoes N-terminal ubiquitination.

Original languageEnglish (US)
Pages (from-to)329-334
Number of pages6
JournalActa neuropathologica
Volume102
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Lewy bodies
  • Parkinson's disease
  • Ubiquitin
  • α-Synuclein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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