Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy - Molecular Imaging Research Center Accéder directement au contenu
Article Dans Une Revue eLife Année : 2019

Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Ali Makky
  • Fonction : Auteur
  • PersonId : 938088
Beat Meier

Résumé

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 $\mathring{A}$ and 3.4 $\mathring{A}$ 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.
Fichier principal
Vignette du fichier
E7AC981A-C8A2-4ACE-ACD4-9EAADA6714BE.pdf (3.46 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

cea-02402414 , version 1 (10-12-2019)
cea-02402414 , version 2 (23-11-2020)

Identifiants

Citer

Ricardo Guerrero-Ferreira, Nicholas M.I. Taylor, Ana-Andreea Arteni, Pratibha Kumari, Daniel Mona, et al.. Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy. eLife, 2019, 8, pp.e48907. ⟨10.7554/eLife.48907⟩. ⟨cea-02402414v2⟩
128 Consultations
140 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More