6SSX

cryo-em structure of alpha-synuclein fibril polymorph 2A

6SSX の概要

• エントリーDOI: 10.2210/pdb6ssx/pdb
• EMDBエントリー: 10307
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: amyloid, parkinson, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 144761.08

構造登録者

Guerrero-Ferreira, R.,Taylor, N.M.I.,Arteni, A.A.,Melki, R.,Meier, B.H.,Bockmann, A.,Bousset, L.,Stahlberg, H. (登録日: 2019-09-09, 公開日: 2019-12-18, 最終更新日: 2024-05-22)

主引用文献

Guerrero-Ferreira, R.,Taylor, N.M.,Arteni, A.A.,Kumari, P.,Mona, D.,Ringler, P.,Britschgi, M.,Lauer, M.E.,Makky, A.,Verasdonck, J.,Riek, R.,Melki, R.,Meier, B.H.,Bockmann, A.,Bousset, L.,Stahlberg, H.
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.
Elife, 8:-, 2019

PubMed Abstract: Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, eLife 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability.

PubMed: 31815671
DOI: 10.7554/eLife.48907

実験手法

ELECTRON MICROSCOPY (2.98 Å)