Release of long-range tertiary interactions potentiates aggregation of natively unstructured α-synuclein
National University of Rosario · Max Planck Institute for Biophysical Chemistry · +1 more institution
Abstract
In idiopathic Parkinson's disease, intracytoplasmic neuronal inclusions (Lewy bodies) containing aggregates of the protein alpha-synuclein (alphaS) are deposited in the pigmented nuclei of the brainstem. The mechanisms underlying the structural transition of innocuous, presumably natively unfolded, alphaS to neurotoxic forms are largely unknown. Using paramagnetic relaxation enhancement and NMR dipolar couplings, we show that monomeric alphaS assumes conformations that are stabilized by long-range interactions and act to inhibit oligomerization and aggregation. The autoinhibitory conformations fluctuate in the range of nanoseconds to micro-seconds corresponding to the time scale of secondary structure…
Citation impact
- FWCI
- 22.15
- Percentile
- 100%
- References
- 47
Authors
7- CWCarlos W. BertonciniCorresponding
National University of Rosario, Max Planck Institute for Biophysical Chemistry, Instituto de Biología Molecular y Celular de Rosario
- YJYoung‐Sang Jung
National University of Rosario, Max Planck Institute for Biophysical Chemistry, Instituto de Biología Molecular y Celular de Rosario
- COClaudio O. Fernández
National University of Rosario, Max Planck Institute for Biophysical Chemistry, Instituto de Biología Molecular y Celular de Rosario
- WHWolfgang Hoyer
National University of Rosario, Max Planck Institute for Biophysical Chemistry, Instituto de Biología Molecular y Celular de Rosario
- CGChristian Griesinger
National University of Rosario, Max Planck Institute for Biophysical Chemistry, Instituto de Biología Molecular y Celular de Rosario
Topics & keywords
- Chemistry
- Biophysics
- Alpha-synuclein
- Protein folding
- Monomer
- Protein aggregation
- Protein tertiary structure
- Folding (DSP implementation)