N-glycosylation of the fourth repeat unit of human tau protein abolishes binding to the C-terminal acidic tau-binding segment of beta-tubulin

Abstract

Tubulin binds to the 18-amino acid repeat units of normal τ protein through several sites. Fluorescence polarization showed τ repeats 1, 3, and 4 bound to an acidic dodecapeptide fragment of tubulin in mM concentrations. From the proposed abnormal modifications of τ in Alzheimer's disease, only addition of an N-acetyl-glucosamine moiety to the potential N-glycosylation site Asn359 abolished the τ-tubulin interaction indicating the seminal role of overutilization of this site during the development of the paired helical filaments.