期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：25
页码：8637-8642
DOI：10.1073/pnas.0712179105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The aggregation of proteins into amyloid fibrils is associated with several neurodegenerative diseases. In Parkinson's disease it is believed that the aggregation of {alpha}-synuclein ({alpha}-syn) from monomers by intermediates into amyloid fibrils is the toxic disease-causative mechanism. Here, we studied the structure of {alpha}-syn in its amyloid state by using various biophysical approaches. Quenched hydrogen/deuterium exchange NMR spectroscopy identified five {beta}-strands within the fibril core comprising residues 35-96 and solid-state NMR data from amyloid fibrils comprising the fibril core residues 30-110 confirmed the presence of {beta}-sheet secondary structure. The data suggest that {beta}1-strand interacts with {beta}2, {beta}2 with {beta}3, {beta}3 with {beta}4, and {beta}4 with {beta}5. High-resolution cryoelectron microscopy revealed the protofilament boundaries of {approx}2 x 3.5 nm. Based on the combination of these data and published structural studies, a fold of {alpha}-syn in the fibrils is proposed and discussed.
