Atomic model of microtubule-bound tau
Posted on: 27 April 2018 , updated on: 2 May 2018
Preprint posted on 16 February 2018
Article now published in Science at http://dx.doi.org/10.1126/science.aat1780
How does Tau stabilize microtubules? Recent preprint uses cryo-EM and atomic modeling to reveal where on the microtubules lattice Tau binds and how its binding stabilizes them; one more piece added to the Tau-microtubule saga.
Selected by Satish Bodakuntla
Categories: bioinformatics, cell biology
Context: Tau is arguably the most important microtubule-associated protein (MAP), possibly due to its physiological role in microtubule regulation and its pathological relevance in several neurodegenerative diseases. Over the years, several studies investigated the mode of tau interaction with microtubules and how the interaction is impaired in disease conditions. Despite these extensive efforts, the molecular mechanisms of tau-microtubule interaction and its effect on microtubule stabilization remain to be fully understood. This preprint from Eva Nogales’ lab has added some valuable information to our understanding of the ‘Tau-microtubule saga’.
Key findings: The authors used state-of-the-art cryo-EM imaging to visualize full-length tau on microtubules. The obtained higher-resolution reconstruction images significantly expanded our previous knowledge on the Tau-microtubule interaction. Some of their key findings are
- The cryo-EM reconstruction of 4.1Å resolution revealed the presence of a narrow, discontinuous density of tau along the protofilament and next to the unstructured C-terminal tails of tubulin. While the observed position of tau is in agreement with previous studies, the density map of tau on microtubules corresponds to a fully extended chain, as opposed to previously proposed α-helical segment.
- Regardless of tau addition to the pre-formed microtubules or to polymerizing tubulin, the authors never observed tau density on the microtubule luminal surface, contradicting previous studies.
- This atomic model clearly showed the importance of the interacting residues in tau-tubulin binding and how they could possibly be mediating the binding.
Why I am interested in this preprint: Personally, I have been interested in the work of Eva Nogales’ lab for some time. This particular study from their lab caught my interest as they worked towards understanding the ‘tau-microtubule’ saga. Earlier studies, despite of their technical limitations, have contributed greatly to our understanding of tau-microtubule binding. In this preprint, taking advantage of state-of-the-art cryo-EM imaging, authors have not only added valuable information to this binding story, but have also revisited and discussed some of the previously published contradicting results.
Questions the work raises: Authors observe the tau density close to the attachment site of unstructured C-terminal tails. This emphasizes a possible role of acidic C-terminal tails in altering the tau affinity. Is it then possible that posttranslational modifications on these acidic tails also influence the tau affinity?
Although the authors succeeded in modeling most of the residues in tau, they could not observe the PGGG motif in the reconstructions. Is it possible that PGGG motif is not involved in the tau-microtubule interaction? Or, like the authors explain, alternatively, is it possible that the motif needs flexibility to bind different conformational states of tubulin?
Related references
X. H. Li, J. A. Culver, E. Rhoades, Tau Binds to Multiple Tubulin Dimers with Helical Structure. J Am Chem Soc 137, 9218-9221 (2015).
S. Kar, J. Fan, M. J. Smith, M. Goedert, L. A. Amos, Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. EMBO J 22, 70-77 (2003).
H. Kadavath et al., Folding of the Tau Protein on Microtubules. Angew Chem Int Ed Engl 54, 10347-10351 (2015).
A. W. P. Fitzpatrick et al., Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547, 185-190 (2017).
J. Al-Bassam, R. S. Ozer, D. Safer, S. Halpain, R. A. Milligan, MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments. J Cell Biol 157, 1187-1196 (2002).
Read preprint
(1 votes) Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the bioinformatics category:
Deep learning-based predictions of gene perturbation effects do not yet outperform simple linear methods
Benjamin Dominik Maier
Functional Diversity of Memory CD8 T Cells is Spatiotemporally Imprinted
Marina Schernthanner
Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium
Rodrigo Senovilla-Ganzo
Also in the cell biology category:
Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer
Teodora Piskova
Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c
Justin Gutkowski
Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Felipe Del Valle Batalla
preLists in the bioinformatics category:
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
| List by | Alex Eve |
Antimicrobials: Discovery, clinical use, and development of resistance
Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.
| List by | Zhang-He Goh |
Also in the cell biology category:
November in preprints – the CellBio edition
This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression
| List by | Felipe Del Valle Batalla et al. |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
| List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
| List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
| List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
| List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
| List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
| List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
| List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
| List by | Joseph Jose Thottacherry |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
| List by | Dey Lab, Amanda Haage |