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

Sharma, Nutan; McLean, Pamela J.; Kawamata, Hibiki; Irizarry, Michael C.; Hyman, Bradley T.

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.

PARKINSON'S disease; FORCE & energy; MOLECULES; PROTEINS; UBIQUITIN; EXTRAPYRAMIDAL disorders

Acta Neuropathologica, 2001, Vol 102, Issue 4, p329

0001-6322

Academic Journal

10.1007/s004010100369