7YMN

Cryo-EM structure of in vitro PHF fibril

Summary for 7YMN

• Entry DOI: 10.2210/pdb7ymn/pdb
• EMDB information: 33934
• Descriptor: Isoform Tau-D of Microtubule-associated protein tau (1 entity in total)
• Functional Keywords: protein fibril, amyloid
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 61125.68

Authors

Li, X.,Liu, C. (deposition date: 2022-07-28, release date: 2022-12-14, Last modification date: 2024-07-03)

Primary citation

Li, X.,Zhang, S.,Liu, Z.,Tao, Y.,Xia, W.,Sun, Y.,Liu, C.,Le, W.,Sun, B.,Li, D.
Subtle change of fibrillation condition leads to substantial alteration of recombinant Tau fibril structure.
Iscience, 25:105645-105645, 2022

PubMed Abstract: assembly of amyloid fibrils that recapitulate those in human brains is very useful for fundamental and applied research on the amyloid formation, pathology, and clinical detection. Recent success in the assembly of Tau fibrils enables the recapitulation of the paired helical filament (PHF) of Tau extracted from brains of patients with Alzheimer's disease (AD). However, following the protocol, we observed that Tau constructs including 297-391 and a mixture of 266-391 (3R)/297-391, which are expected to predominantly form PHF-like fibrils, form highly heterogeneous fibrils instead. Moreover, the seemingly PHF-like fibril formed by Tau 297-391 exhibits a distinctive atomic structure with a spindle-like fold, that is neither PHF-like or similar to any known Tau fibril structures revealed by cryo-electron microscopy (cryo-EM). Our work highlights the high sensitivity of amyloid fibril formation to subtle conditional changes and suggests high-resolution structural characterization to assembled fibrils prior to further laboratory use.

PubMed: 36505939
DOI: 10.1016/j.isci.2022.105645

Experimental method

ELECTRON MICROSCOPY (3.46 Å)