Microtubule-binding core of the tau protein
Name
sciadv.abo4459.pdf
Description
Published version
Size
3.61 MB
Format
Adobe PDF
Checksum (MD5)
c5443b6e8f4ba841998b404e3d796a7d
Author(s)
El Mammeri, Nadia
Dregni, Aurelio J
Duan, Pu
Wang, Harrison K
Hong, Mei
Date Issued
July 20, 2022
Journal
Science Advances
Publisher
American Association for the Advancement of Science
Citation
Nadia El Mammeri et al., Microtubule-binding core of the tau protein. Sci. Adv. 8, eabo4459 (2022).
Version
Final published version
Abstract
The protein tau associates with microtubules to maintain neuronal health. Posttranslational modifications of tau interfere with this binding, leading to tau aggregation in neurodegenerative disorders. Here, we use solid-state nuclear magnetic resonance (NMR) to investigate the structure of the microtubule-binding domain of tau. Wild-type tau that contains four microtubule-binding repeats and a pseudorepeat R′ is studied. Complexed with taxol-stabilized microtubules, the immobilized residues exhibit well-resolved two-dimensional spectra that can be assigned to the amino-terminal region of R4 and the R′ domain. When tau coassembles with tubulin to form unstable microtubules, the R′ signals remain, whereas the R4 signals disappear, indicating that R′ remains immobilized, whereas R4 becomes more mobile. Therefore, R′ outcompetes the other four repeats to associate with microtubules. These NMR data, together with previous cryo–electron microscopy densities, indicate an extended conformation for microtubule-bound R′. R′ contains the largest number of charged residues among all repeats, suggesting that charge-charge interaction drives tau-microtubule association.
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Creative Commons Attribution-NonCommercial
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DOI of Published Version
https://doi.org/10.1126/sciadv.abo4459
