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Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
Defining long-range order and local disorder in native alpha-synuclein using residual dipolar couplings
Pau Bernadó1, Carlos W Bertoncini, Christian Griesinger
1Institute de Biologie Structurale Jean-Pierre Ebel, CNRS-CEA-UJF, 41 rue Jules Horowitz, 38027-Grenoble Cedex, France.
Journal of the American Chemical Society
|December 22, 2005
Summary
This study reveals how residual dipolar couplings (RDCs) can detect long-range structural order in intrinsically unstructured proteins. This breakthrough aids in understanding proteins like alpha-Synuclein linked to Parkinson's disease.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Intrinsically unstructured proteins (IUPs) are crucial in biological processes and disease.
- Studying IUPs requires understanding their dynamic, ensemble nature.
- Residual dipolar couplings (RDCs) are sensitive to protein dynamics on millisecond timescales.
Purpose of the Study:
- To develop a novel interpretation of RDCs for unfolded proteins.
- To simultaneously define long-range structural order and local conformational sampling in IUPs.
- To characterize the structure and dynamics of alpha-Synuclein (alphaS), a protein implicated in Parkinson's disease.
Main Methods:
- Utilized a novel interpretation of residual dipolar couplings (RDCs).
- Applied RDC analysis to study the structure and dynamics of alpha-Synuclein (alphaS).
- Developed a structural model combining local conformational fluctuations and long-range contacts.
Main Results:
- Demonstrated that RDCs can simultaneously report on long-range order and local sampling in unfolded proteins.
- Unambiguously detected populated conformers with long-range contacts in alphaS.
- Showed that both local fluctuations and long-range contacts are essential for describing alphaS RDCs.
Conclusions:
- The novel RDC interpretation provides new insights into the conformational landscape of IUPs.
- This approach reveals long-range order in highly flexible systems, previously undetected.
- Enhanced understanding of alphaS structure and dynamics, relevant to Parkinson's disease.
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