Chemically synthesized 182–235 segment of tau protein and analogue peptides are efficient in vitro microtubule assembly inducers of low apparent sequence specificity

Abstract

A 54-amino acid peptide reproducing the first and second repeats and intervening spacer sequence of the tubulin binding motif (residues 182–235) of murine tau protein, and several congeners representing different degrees of sequence scrambling have been prepared by solid phase methods and fully characterized chemically. These double-repeat peptides have been shown to induce microtubule formation at concentrations about one order of magnitude lower than single-repeat controls, under conditions close to the critical concentration needed for tubulin self-assembly. On the other hand, partial loss of microtubule-inducing capacity was observed for peptides with primary structures increasingly disorganized with respect to the canonical peptide, These results call into question the assumption that a high degree of primary structure specificity is involved in the tau-tubulin interaction leading to in vitro microtubule formation