7E0F

CryoEM structure of G51D alpha-synuclein amyloid fibril

Summary for 7E0F

• Entry DOI: 10.2210/pdb7e0f/pdb
• EMDB information: 30931
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: amyloid fibril, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 87204.88

Authors

Sun, Y.P.,Long, H.F.,Xia, W.C.,Liu, C. (deposition date: 2021-01-27, release date: 2021-10-06, Last modification date: 2024-06-05)

Primary citation

Sun, Y.,Long, H.,Xia, W.,Wang, K.,Zhang, X.,Sun, B.,Cao, Q.,Zhang, Y.,Dai, B.,Li, D.,Liu, C.
The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type alpha-synuclein.
Nat Commun, 12:6252-6252, 2021

PubMed Abstract: α-Synuclein (α-Syn) can form different fibril strains with distinct polymorphs and neuropathologies, which is associated with the clinicopathological variability in synucleinopathies. How different α-syn fibril strains are produced and selected under disease conditions remains poorly understood. In this study, we show that the hereditary mutation G51D induces α-syn to form a distinct fibril strain in vitro. The cryogenic electron microscopy (cryo-EM) structure of the G51D fibril strain was determined at 2.96 Å resolution. The G51D fibril displays a relatively small and extended serpentine fold distinct from other α-syn fibril structures. Moreover, we show by cryo-EM that wild-type (WT) α-syn can assembly into the G51D fibril strain via cross-seeding with G51D fibrils. Our study reveals a distinct structure of G51D fibril strain triggered by G51D mutation but feasibly adopted by both WT and G51D α-syn, which suggests the cross-seeding and strain selection of WT and mutant α-syn in familial Parkinson's disease (fPD).

PubMed: 34716315
DOI: 10.1038/s41467-021-26433-2

Experimental method

ELECTRON MICROSCOPY (3.02 Å)