Team 9 and PINT are glad to see Romain La Rocca's main PhD paper is finally out in the International Journal of Biological Macromolecules. Entitled "Identification of the three zinc-binding sites on tau protein", it is authored by Romain Rocca, Philipp Tsvetkov, Andrey Golovin, Diane Allegro, Pascale Barbier, Soazig Malesinski, Françoise Guerlesquin, and François Devred
Tau protein has been extensively studied due to its key roles in microtubular cytoskeleton regulation and in the formation of aggregates found in some neurodegenerative diseases. Recently it has been shown that zinc is able to induce tau aggregation by interacting with several binding sites. However, the precise location of these sites and the molecular mechanism of zinc-induced aggregation remain unknown. Here we used Nuclear Magnetic Resonance (NMR) to identify zinc binding sites on tau. These experiments revealed three distinct zinc binding sites on tau, located in the N-terminal part, the repeat region and the C-terminal part. Further analysis enabled us to show that the N-terminal and the C-terminal sites are independent of each other. Using molecular simulations, we proposed a model of each site in a complex with zinc. Given the clinical importance of zinc in tau aggregation, our findings pave the way for designing potential therapies for tauopathies.
Editor's website : https://www.sciencedirect.com/science/article/abs/pii/S0141813022007620