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Conserved core of amyloid fibrils of wild type and A30P mutant α‐synuclein
Author(s) -
Cho MinKyu,
Kim HaiYoung,
Fernandez Claudio O.,
Becker Stefan,
Zweckstetter Markus
Publication year - 2011
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.570
Subject(s) - fibril , amyloid (mycology) , biophysics , chemistry , mutant , mutation , amyloid fibril , crystallography , hydrogen–deuterium exchange , magic angle spinning , wild type , nuclear magnetic resonance spectroscopy , amyloid β , biochemistry , biology , stereochemistry , hydrogen , gene , medicine , inorganic chemistry , disease , organic chemistry , pathology
The major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein α‐synuclein (aS). Here we investigated if the disease‐related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuterium exchange coupled to NMR spectroscopy and performed two‐dimensional proton‐detected high‐resolution magic angle spinning experiments. The combined data indicate that the A30P mutation does not cause changes in the number, location and overall arrangement of β‐strands in amyloid fibrils of aS. At the same time, several residues within the fibrillar core retain nano‐second dynamics. We conclude that the increased pathogenicity related to the familial A30P mutation is unlikely to be caused by a mutation‐induced change in the conformation of aS aggregates.