6OSM

Cryo-EM structure of the N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103

Summary for 6OSM

• Entry DOI: 10.2210/pdb6osm/pdb
• EMDB information: 20183 20186 20186
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: c-terminal alpha-synuclein truncation, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 10
• Total formula weight: 144761.08

Authors

Xiaodan, N.,Ryan, P.M.,Jiansen, J.,Jennifer, C.L. (deposition date: 2019-05-01, release date: 2019-09-25, Last modification date: 2024-03-20)

Primary citation

Ni, X.,McGlinchey, R.P.,Jiang, J.,Lee, J.C.
Structural Insights into alpha-Synuclein Fibril Polymorphism: Effects of Parkinson's Disease-Related C-Terminal Truncations.
J.Mol.Biol., 431:3913-3919, 2019

PubMed Abstract: 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.

PubMed: 31295458
DOI: 10.1016/j.jmb.2019.07.001

Experimental method

ELECTRON MICROSCOPY (3.4 Å)