title: A discrete repeated sequence defines a tubulin binding domain on microtubule-associated protein tau.
abstract: The protein domain responsible for the interaction of tau with tubulin has been identified. Biophysical studies indicated that the synthetic peptide Val187-Gly204 (VRSKIG-STENLKHQPGGG) from the repetitive sequence on tau binds to two sites on the tubulin heterodimer and to one site on each of the microtubule-associated protein-interacting C-terminal tubulin peptides alpha(430-441) and beta(422-434). The binding data showed a relatively stronger interaction of Val187-Gly204 with beta(422-434) as compared to that with alpha(430-441). The interaction of this tau peptide with either alpha or beta tubulin peptides appears to be associated with conformational changes in both the tau and the tubulin peptides. The beta tubulin peptide also appears to induce a structural change of tau fragment Val218-Gly235. Interestingly, tau peptides Val187-Gly204 and Val218-Gly235 induced tubulin self-assembly in a cold-reversible fashion, and incorporated into the assembled polymers. The specificity of the interaction of the tau peptide was supported by the competition of tau protein for the interaction with the tubulin polymer. In addition, the tau peptide appears to contain the principal antigenic determinant(s) recognized by anti-idiotypic antibodies that react with the tubulin binding domains on microtubule-associated proteins. The present findings together with the demonstration of the presence of multiple sites for the binding of the alpha(430-441) and beta(422-434) tubulin fragments to tau, and the existence of repetitive sequences on tau, strongly support the hypothesis that the region of tau defined by the repetitive sequences is involved in its interaction with tubulin.
authors.affiliation: University of Colorado Health Sciences Center, Denver 80262.
authors.forename: R B
authors.initials: RB
authors.lastname: Maccioni
authors.forename: J C
authors.initials: JC
authors.lastname: Vera
authors.forename: J
authors.initials: J
authors.lastname: Dominguez
authors.forename: J
authors.initials: J
authors.lastname: Avila
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002417:Cattle; D007700:Kinetics; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D014404:Tubulin / Q000378:metabolism* / Q000648:ultrastructure; D016875:tau Proteins
chemical_list: D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D014404:Tubulin; D016875:tau Proteins