10MR

VT II tau filament from VT Case 1

Summary for 10MR

• Entry DOI: 10.2210/pdb10mr/pdb
• EMDB information: 49629 75292
• Descriptor: Microtubule-associated protein tau (1 entity in total)
• Functional Keywords: microtubule-associated protein, structural protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 18
• Total formula weight: 147319.42

Authors

Watanabe, R.,Lee, E.B. (deposition date: 2026-01-28, release date: 2026-09-02, Last modification date: 2026-09-16)

Primary citation

Watanabe, R.,Creekmore, B.C.,Darwich, N.F.,Smith, C.L.,Xu, H.,Baltazar, A.,Salphati, S.,Changolkar, L.,Hoxha, K.,Zhang, B.,O'Rourke, C.M.,Burslem, G.M.,Lee, V.M.,Chang, Y.W.,Lee, E.B.
Repositioning of polyubiquitin alters the pathologic tau filament structure.
Nat.Struct.Mol.Biol., 2026

PubMed Abstract: Structurally diverse tau filaments form proteinaceous aggregates in a heterogeneous group of neurodegenerative diseases called tauopathies. The factors extrinsic to the highly ordered core structure that influence tau filament stability are not well understood. Here, we found that polyubiquitinated tau filaments from Alzheimer disease and vacuolar tauopathy human brain tissue exhibit distinct seeding patterns in mice, in association with differences in tau filament ultrastructure determined by cryo-electron microscopy. Chemical modulation of the polarity of polyubiquitin adjacent to the tau core with the small molecule ubistatin B resulted in the repositioning of poorly structured densities toward positively charged residues on the highly structured core filament, leading to shifting of the protofilament-protofilament interface of certain vacuolar tauopathy tau filaments. These results suggest that the structure of tau filaments that are associated with different seeding activities in vivo can be influenced by post-translational modifications.

PubMed: 42675211
DOI: 10.1038/s41594-026-01879-4

Experimental method

ELECTRON MICROSCOPY (3.14 Å)