English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Familial mutants of α-synuclein with increased neurotoxicity have a destabilized conformation

MPS-Authors
/persons/resource/persons14841

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

/persons/resource/persons15063

Fernandez,  C. O.
Department of NMR Based Structural 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)

233392.pdf
(Publisher version), 0B

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

Bertoncini, C. W., Fernandez, C. O., Griesinger, C., Jovin, T. M., & Zweckstetter, M. (2005). Familial mutants of α-synuclein with increased neurotoxicity have a destabilized conformation. Journal of Biological Chemistry, 280, 30649-30652. Retrieved from http://www.jbc.org/cgi/content/full/280/35/30649?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=280&firstpage=30649&resourcetype=HWCIT.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0012-E826-D
Abstract
A30P and A53T mutations of the presynaptic protein α-synuclein are associated with familial forms of Parkinson’s disease. NMR spectroscopy demonstrates that Parkinsonism-linked mutations greatly perturb specific tertiary interactions essential for the native state of α-synuclein. However, α-synuclein is not completely unfolded, but exhibits structural fluctuations on the time scale of secondary structure formation, and loses its native conformation gradually when protein stability decreases. The redistribution of the ensemble of α-synuclein conformers may underlie toxic gain-of-function by fostering self-association and altered binding affinity to ligands and receptors.