Artículos de revistas
Tau induces ring and microtubule formation from αβ-tubulin dimers under nonassembly conditions
Fecha
2004Registro en:
Biochemistry, Volumen 43, Issue 32, 2018, Pages 10520-10531
00062960
10.1021/bi0493160
Autor
Devred, François
Barbier, Pascale
Douillard, Soazig
Monasterio Opazo, Octavio
Andreu, José Manuel
Peyrot, Vincent
Institución
Resumen
Tau is a neuronal microtubule-associated protein that plays a central role in many cellular processes, both physiological and pathological, such as axons stabilization and Alzheimer's disease. Despite extensive studies, very little is known about the detailed molecular basis of tau binding to microtubules. We used the four-repeat recombinant htau40 and tubulin dimers to show for the first time that tau is able to induce both microtubule and ring formation from 6S αβ tubulin in phosphate buffer without added magnesium (nonassembly conditions). The amount of microtubules or rings formed was protein concentration-, temperature-, and nucleotide-dependent. By means of biophysical approaches, we showed that tau binds to tubulin without global-folding change, detectable by circular dichroism. We also demonstrated that the tau-tubulin interaction follows a ligand-mediated elongation process, with two tau-binding site per tubulin dimer. Moreover, using a tubulin recombinant α-tubulin C-terminal