9CKK

Cryo-EM structure of acetylated alpha-synuclein A53T fibril - polymorph A

Summary for 9CKK

• Entry DOI: 10.2210/pdb9ckk/pdb
• EMDB information: 45650
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: amyloid, neurodegeneration, aggregrate, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 8
• Total formula weight: 116049.09

Authors

Ansari, S.,Li, Y.,Frederick, K.K. (deposition date: 2024-07-09, release date: 2025-06-25)

Primary citation

Ansari, S.,Lagasca, D.,Dumarieh, R.,Xiao, Y.,Krishna, S.,Li, Y.,Frederick, K.K.
In cell NMR reveals cells selectively amplify and structurally remodel amyloid fibrils.
Biorxiv, 2024

PubMed Abstract: Amyloid forms of α-synuclein adopt different conformations depending on environmental conditions. Advances in structural biology have accelerated fibril characterization. However, it remains unclear which conformations predominate in biological settings because current methods typically not only require isolating fibrils from their native environments, but they also do not provide insight about flexible regions. To address this, we characterized α-syn amyloid seeds and used sensitivity enhanced nuclear magnetic resonance to investigate the amyloid fibrils resulting from seeded amyloid propagation in different settings. We found that the amyloid fold and conformational preferences of flexible regions are faithfully propagated and in cellular lysates. However, seeded propagation of amyloids inside cells led to the minority conformation in the seeding population becoming predominant and more ordered, and altered the conformational preferences of flexible regions. The examination of the entire ensemble of protein conformations in biological settings that is made possible with this approach may advance our understanding of protein misfolding disorders and facilitate structure-based drug design efforts.

PubMed: 39314304
DOI: 10.1101/2024.09.09.612142

Experimental method

ELECTRON MICROSCOPY (2.21 Å)