Premium
Structural characterization of α‐synuclein in an aggregation prone state
Author(s) -
Cho MinKyu,
Nodet Gabrielle,
Kim HaiYoung,
Jensen Malene R.,
Bernado Pau,
Fernandez Claudio O.,
Becker Stefan,
Blackledge Martin,
Zweckstetter Markus
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.194
Subject(s) - alpha synuclein , chemistry , nuclear magnetic resonance spectroscopy , characterization (materials science) , crystallography , biophysics , stereochemistry , biology , materials science , nanotechnology , parkinson's disease , medicine , disease , pathology
The relation of α‐synuclein (αS) aggregation to Parkinson's disease has long been recognized, but the pathogenic species and its molecular properties have yet to be identified. To obtain insight into the properties of αS in an aggregation‐prone state, we studied the structural properties of αS at acidic pH using NMR spectroscopy and computation. NMR demonstrated that αS remains natively unfolded at lower pH, but secondary structure propensities were changed in proximity to acidic residues. The ensemble of conformations of αS at acidic pH is characterized by a rigidification and compaction of the Asp and Glu‐rich C‐terminal region, an increased probability for proximity between the NAC‐region and the C‐terminal region and a lower probability for interactions between the N‐ and C‐terminal regions.