Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1073/pnas.97.10.5129 |
| Titel (primär) | Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming β structure |
| Autor | von Bergen, M.; Friedhoff, P.; Biernat, J.; Heberle, J.; Mandelkow, E.-M.; Mandelkow, E. |
| Quelle | Proceedings of the National Academy of Sciences of the United States of America |
| Erscheinungsjahr | 2000 |
| Department | PROTEOM |
| Band/Volume | 97 |
| Heft | 10 |
| Seite von | 5129 |
| Seite bis | 5134 |
| Sprache | englisch |
| Abstract | We have searched for a minimal interaction motif in tau protein that supports the aggregation into Alzheimer-like paired helical filaments. Digestion of the repeat domain with different proteases yields a GluC-induced fragment comprising 43 residues (termed PHF43), which represents the third repeat of tau plus some flanking residues. This fragment self assembles readily into thin filaments without a paired helical appearance, but these filaments are highly competent to nucleate bona fide PHFs from full-length tau. Probing the interactions of PHF43 with overlapping peptides derived from the full tau sequence yields a minimal hexapeptide interaction motif of (306)VQIVYK(311) at the beginning of the third internal repeat. This motif coincides with the highest predicted beta-structure potential in tau. CD and Fourier transform infrared spectroscopy shows that PHF43 acquires pronounced beta structure in conditions of self assembly. Point mutations in the hexapeptide region by proline-scanning mutagenesis prevent the aggregation. The data indicate that PHF assembly is initiated by a short fragment containing the minimal interaction motif forming a local beta structure embedded in a largely random-coil protein. |
| dauerhafte UFZ-Verlinkung | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=7733 |
| von Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E.-M., Mandelkow, E. (2000): Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming β structure Proc. Natl. Acad. Sci. U.S.A. 97 (10), 5129 - 5134 10.1073/pnas.97.10.5129 |
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