Common antigenic determinants of the tubulin binding domains of the microtubule-associated proteins MAP-2 and tau.
The structural-functional aspects of the tubulin binding domain on the microtubule-associated protein MAP-2, and its relationship with the tubulin binding domain on tau, were studied using anti-idiotypic antibodies that react specifically with the epitope(s) on MAPs involved in their interaction with tubulin in addition to other tau and MAP-2 specific antibodies. Previous studies showed that MAP-2 and tau share common binding sites on tubulin defined by the peptide sequences alpha (430-441) and beta (422-434) of tubulin subunits. Furthermore, binding experiments revealed the existence of multiple sites for the interaction of the alpha- and beta-tubulin peptides with MAP-2 and tau. Most recent studies showed that the synthetic tau peptide Val187-Gly204 (VRSKIGSTENLKHQPGGG) from the repetitive sequence on tau defines a tubulin binding site on tau. Our present immunological studies using anti-idiotypic antibodies which interact with the synthetic tau peptide and antibodies against the Val187-Gly204 tau peptide indicate that MAP-2 and tau share common antigenic determinants at the level of their respective tubulin binding domains. These antigenic determinants appear to be present in the 35 kDa tubulin binding fragment of MAP-2 and in 18-20 kDa chymotryptic fragments containing the tubulin binding site(s) on MAP-2. These findings, along with structural information on these proteins, provide strong evidence in favor of the hypothesis that tubulin binding domains on MAP-2 and tau share similar structural features.
International Center for Cancer and Developmental Biology, Santiago, Chile.
A
A
Rivas-Berríos
M A
MA
Hernández
J
J
Domínguez
J
J
Avila
R B
RB
Maccioni
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001665:Binding Sites; D002417:Cattle; D000939:Epitopes; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010449:Peptide Mapping; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins
D000888:Antibodies, Anti-Idiotypic; D000939:Epitopes; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D014404:Tubulin; D016875:tau Proteins