6QJM

Cryo-EM structure of heparin-induced 2N4R tau twister filaments

Summary for 6QJM

• Entry DOI: 10.2210/pdb6qjm/pdb
• EMDB information: 4564
• Descriptor: Microtubule-associated protein tau (1 entity in total)
• Functional Keywords: recombinant tau protein, heparin, filament, cross-beta structure, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 15567.24

Authors

Zhang, W.,Falcon, B.,Murzin, A.G.,Fan, J.,Crowther, R.A.,Goedert, M.,Scheres, S.H.W. (deposition date: 2019-01-24, release date: 2019-02-27, Last modification date: 2024-05-15)

Primary citation

Zhang, W.,Falcon, B.,Murzin, A.G.,Fan, J.,Crowther, R.A.,Goedert, M.,Scheres, S.H.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's diseases.
Elife, 8:-, 2019

PubMed Abstract: Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's diseases. Here, we used cryo- and immuno- electron microscopy to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 2N4R tau assembles into multiple types of filaments, and the structures of three types reveal similar 'kinked hairpin' folds, in which the second and third repeats pack against each other. 2N3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack in a parallel manner. The heparin-induced tau filaments differ from those of Alzheimer's or Pick's disease, which have larger cores with different repeat compositions. Our results illustrate the structural versatility of amyloid filaments, and raise questions about the relevance of in vitro assembly.

PubMed: 30720432
DOI: 10.7554/eLife.43584

Experimental method

ELECTRON MICROSCOPY (3.3 Å)