Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Novel tau filament fold in corticobasal degeneration, a four-repeat tauopathy

Wenjuan Zhang, Airi Tarutani, Kathy L. Newell, Alexey G. Murzin, Tomoyasu Matsubara, Benjamin Falcon, Ruben Vidal, Holly J. Garringer, Yang Shi, Takeshi Ikeuchi, Shigeo Murayama, Bernardino Ghetti, Masato Hasegawa, Michel Goedert, View ORCID ProfileSjors H.W. Scheres
doi: https://doi.org/10.1101/811703
Wenjuan Zhang
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Airi Tarutani
2Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathy L. Newell
3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexey G. Murzin
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomoyasu Matsubara
4Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin Falcon
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruben Vidal
3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Holly J. Garringer
3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yang Shi
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeshi Ikeuchi
5Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shigeo Murayama
4Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernardino Ghetti
3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masato Hasegawa
2Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michel Goedert
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sjors H.W. Scheres
1MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sjors H.W. Scheres
  • For correspondence: scheres@mrc-lmb.cam.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Corticobasal degeneration (CBD) is a neurodegenerative tauopathy that is characterised by motor and cognitive disturbances (1–3). A higher frequency of the H1 haplotype of MAPT, the tau gene, is present in cases of CBD than in controls (4, 5) and genome-wide association studies have identified additional risk factors (6). By histology, astrocytic plaques are diagnostic of CBD (7, 8), as are detergent-insoluble tau fragments of 37 kDa by SDS-PAGE (9). Like progressive supranuclear palsy (PSP), globular glial tauopathy (GGT) and argyrophilic grain disease (AGD) (10), CBD is characterised by abundant filamentous tau inclusions that are made of isoforms with four microtubule-binding repeats (4R) (11–15). This distinguishes 4R tauopathies from Pick’s disease, filaments of which are made of three-repeat (3R) tau isoforms, and from Alzheimer’s disease and chronic traumatic encephalopathy (CTE), where both 3R and 4R tau isoforms are found in the filaments (16). Here we report the structures of tau filaments extracted from the brains of three individuals with CBD using electron cryo-microscopy (cryo-EM). They were identical between cases, but distinct from those of Alzheimer’s disease, Pick’s disease and CTE (17–19). The core of CBD filaments comprises residues K274-E380 of tau, spanning the last residue of R1, the whole of R2, R3 and R4, as well as 12 amino acids after R4. It adopts a novel four-layered fold, which encloses a large non-proteinaceous density. The latter is surrounded by the side chains of lysine residues 290 and 294 from R2 and 370 from the sequence after R4. CBD is the first 4R tauopathy with filaments of known structure.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted October 21, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Novel tau filament fold in corticobasal degeneration, a four-repeat tauopathy
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Novel tau filament fold in corticobasal degeneration, a four-repeat tauopathy
Wenjuan Zhang, Airi Tarutani, Kathy L. Newell, Alexey G. Murzin, Tomoyasu Matsubara, Benjamin Falcon, Ruben Vidal, Holly J. Garringer, Yang Shi, Takeshi Ikeuchi, Shigeo Murayama, Bernardino Ghetti, Masato Hasegawa, Michel Goedert, Sjors H.W. Scheres
bioRxiv 811703; doi: https://doi.org/10.1101/811703
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Novel tau filament fold in corticobasal degeneration, a four-repeat tauopathy
Wenjuan Zhang, Airi Tarutani, Kathy L. Newell, Alexey G. Murzin, Tomoyasu Matsubara, Benjamin Falcon, Ruben Vidal, Holly J. Garringer, Yang Shi, Takeshi Ikeuchi, Shigeo Murayama, Bernardino Ghetti, Masato Hasegawa, Michel Goedert, Sjors H.W. Scheres
bioRxiv 811703; doi: https://doi.org/10.1101/811703

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (2440)
  • Biochemistry (4803)
  • Bioengineering (3340)
  • Bioinformatics (14724)
  • Biophysics (6658)
  • Cancer Biology (5188)
  • Cell Biology (7455)
  • Clinical Trials (138)
  • Developmental Biology (4378)
  • Ecology (6904)
  • Epidemiology (2057)
  • Evolutionary Biology (9943)
  • Genetics (7357)
  • Genomics (9550)
  • Immunology (4583)
  • Microbiology (12730)
  • Molecular Biology (4960)
  • Neuroscience (28422)
  • Paleontology (199)
  • Pathology (810)
  • Pharmacology and Toxicology (1400)
  • Physiology (2031)
  • Plant Biology (4521)
  • Scientific Communication and Education (980)
  • Synthetic Biology (1305)
  • Systems Biology (3922)
  • Zoology (731)