Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's disease
Alexey G. Murzin,
R. Anthony Crowther,
Sjors H.W. Scheres
Posted 13 Nov 2018
bioRxiv DOI: 10.1101/468892 (published DOI: 10.7554/eLife.43584)
Posted 13 Nov 2018
The assembly of microtubule-associated protein tau into abundant filamentous inclusions underlies a range of neurodegenerative diseases. The finding that tau filaments adopt different conformations in Alzheimer's and Pick's diseases raises the question of what kinds of structures of tau filaments form in vitro. Here, we used electron cryo-microscopy (cryo-EM) and negative-stain immuno-gold electron microscopy (immuno-EM) 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. 4R tau assembles into at least four different types of filaments. Cryo-EM structures of three types of 4R filaments reveal similar "kinked hairpin" folds, in which the second and third repeats pack against each other. 3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack against each other in a parallel, yet asymmetric, manner. None of the heparin-induced tau filaments resemble those of Alzheimer's or Pick's disease, which have larger cores with different repeat compositions. Our results indicate that tau filaments are structurally versatile, and raise questions about the relevance of in vitro assembled amyloids.
- Downloaded 1,235 times
- Download rankings, all-time:
- Site-wide: 8,149 out of 89,568
- In biophysics: 246 out of 3,903
- Year to date:
- Site-wide: 42,643 out of 89,568
- Since beginning of last month:
- Site-wide: 47,512 out of 89,568
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!