PDBsum entry 6osm

Protein fibril

PDB id: 6osm

Contents

Protein chains

(+ 4 more) 60 a.a.

PDB id:

6osm

Name:

Protein fibril

Title:

Cryo-em structure of the n-terminally acetylated c-terminal alpha- synuclein truncation ac1-103

Structure:

Alpha-synuclein. Chain: a, b, c, d, e, f, g, h, i, j. Synonym: non-a beta component of ad amyloid,non-a4 component of amyloid precursor,nacp. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: snca, nacp, park1. Expressed in: escherichia coli. Expression_system_taxid: 562

Authors:

N.Xiaodan,P.M.Ryan,J.Jiansen,C.L.Jennifer

Key ref:

X.Ni et al. (2019). Structural Insights into α-Synuclein Fibril Polymorphism: Effects of Parkinson's Disease-Related C-Terminal Truncations. J Mol Biol, 431, 3913-3919. PubMed id: 31295458 DOI: 10.1016/j.jmb.2019.07.001

Date:

01-May-19 Release date: 25-Sep-19

Protein chains

P37840  (SYUA_HUMAN) -  Alpha-synuclein from Homo sapiens

Seq: 140 a.a.

Struc: 60 a.a.

DOI no: 10.1016/j.jmb.2019.07.001

J Mol Biol 431:3913-3919 (2019)

PubMed id: 31295458

Structural Insights into α-Synuclein Fibril Polymorphism: Effects of Parkinson's Disease-Related C-Terminal Truncations.

X.Ni, R.P.McGlinchey, J.Jiang, J.C.Lee.

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.