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PDBsum entry 6osm
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Protein fibril
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PDB id
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6osm
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References listed in PDB file
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Key reference
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Title
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Structural insights into α-Synuclein fibril polymorphism: effects of parkinson'S disease-Related c-Terminal truncations.
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Authors
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X.Ni,
R.P.Mcglinchey,
J.Jiang,
J.C.Lee.
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Ref.
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J Mol Biol, 2019,
431,
3913-3919.
[DOI no: ]
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PubMed id
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Abstract
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Lewy bodies, hallmarks of Parkinson's disease, contain C-terminally truncated
(ΔC) α-synuclein (α-syn). Here, we report fibril structures of three
N-terminally acetylated (Ac) α-syn constructs, Ac1-140, Ac1-122, and Ac1-103,
solved by cryoelectron microscopy. Both ΔC-α-syn variants exhibited faster
aggregation kinetics, and Ac1-103 fibrils efficiently seeded the full-length
protein, highlighting their importance in pathogenesis. Interestingly, fibril
helical twists increased upon the removal of C-terminal residues and can be
propagated through cross-seeding. Compared to that of Ac1-140, increased
electron densities were seen in the N-terminus of Ac1-103, whereas the
C-terminus of Ac1-122 appeared more structured. In accord, the respective
termini of ΔC-α-syn exhibited increased protease resistance. Despite similar
amyloid core residues, distinctive features were seen for both Ac1-122 and
Ac1-103. Particularly, Ac1-103 has the tightest packed core with an additional
turn, likely attributable to conformational changes in the N-terminal region.
These molecular differences offer insights into the effect of C-terminal
truncations on α-syn fibril polymorphism.
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