English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Release of long-range tertiary interactions potentiates aggregation of natively unstructured α-synuclein

MPS-Authors
/persons/resource/persons14841

Bertoncini,  C. W.
Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15288

Jung,  Y. S.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

Fernandez,  C. O.
Max Planck Society;

/persons/resource/persons15252

Hoyer,  W.
Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15147

Griesinger,  C.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15286

Jovin,  T. M.
Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons16093

Zweckstetter,  M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

207200.pdf
(Publisher version), 0B

Supplementary Material (public)
There is no public supplementary material available
Citation

Bertoncini, C. W., Jung, Y. S., Fernandez, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., et al. (2005). Release of long-range tertiary interactions potentiates aggregation of natively unstructured α-synuclein. Proceedings of the National Academy of Sciences of the United States of America, 102(5), 1430-1435. Retrieved from http://www.pnas.org/content/102/5/1430.full.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0012-EA11-D
Abstract
In idiopathic Parkinson’s disease, intracytoplasmic neuronal inclusions (Lewy bodies) containing aggregates of the protein α-synuclein (αS) are deposited in the pigmented nuclei of the brainstem. The mechanisms underlying the structural transition of innocuous, presumably natively unfolded, αS to neurotoxic forms are largely unknown. Using paramagnetic relaxation enhancement and NMR dipolar couplings, we show that monomeric αS 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 microseconds corresponding to the time scale of secondary structure formation during folding. Polyamine binding and or temperature increase, conditions that induce aggregation in vitro, release this inherent tertiary structure, leading to a completely unfolded conformation that associates readily. Stabilization of the native, autoinhibitory structure of αS constitutes a potential strategy for reducing or inhibiting oligomerization and aggregation in Parkinson’s disease.