6SSX

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

Summary for 6SSX

• Entry DOI: 10.2210/pdb6ssx/pdb
• EMDB information: 10307
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: amyloid, parkinson, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 10
• Total formula weight: 144761.08

Authors

Guerrero-Ferreira, R.,Taylor, N.M.I.,Arteni, A.A.,Melki, R.,Meier, B.H.,Bockmann, A.,Bousset, L.,Stahlberg, H. (deposition date: 2019-09-09, release date: 2019-12-18, Last modification date: 2024-05-22)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.98 Å)