Chemically synthesized 182-235 segment of tau protein and analogue peptides are efficient in vitro microtubule assembly inducers of low apparent sequence specificity.
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.
Novella
I S
IS
Departament de Química Orgànica, Universitat de Barcelona, Spain.
Andreu
J M
JM
Andreu
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D007202:Indicators and Reagents; D007700:Kinetics; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013997:Time Factors; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016875:tau Proteins / Q000138:chemical synthesis* / Q000494:pharmacology*
D007202:Indicators and Reagents; D010446:Peptide Fragments; D010455:Peptides; D014404:Tubulin; D016875:tau Proteins; C077510:tau protein (182-235)