Tau mutants bind tubulin heterodimers with enhanced affinity.

ABSTRACT: Tau is a microtubule binding protein that forms pathological aggregates in the brain in Alzheimer's disease and other tauopathies. Disease etiology is thought to arise from loss of native interactions between tau and microtubules, as well as from gain of toxicity tied to tau aggregation, although neither mechanism is well understood. Here we investigate the link between function and disease using disease-associated and disease-motivated mutants of tau. We find that mutations to highly conserved proline residues in repeats 2 and 3 of the microtubule binding domain have differential effects on tau binding to tubulin and the capacity of tau to enhance tubulin polymerization. Notably, mutations to these residues result in an increased affinity for tubulin dimers while having a negligible effec

SUBMITTER: Elbaum-Garfinkle S 

PROVIDER: S-EPMC4035965 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature