Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias
Autor Barghorn, S.; Zheng-Fischhofer, Q.; Ackmann, M.; Biernat, J.; von Bergen, M.; Mandelkow, E.-M.; Mandelkow, E.;
Journal / Serie Biochemistry
Erscheinungsjahr 2000
Department PROTEOM;
Band/Volume 39
Heft 38
Sprache englisch;
Abstract We have studied biochemical and structural parameters of several missense and deletion mutants of tau protein (G272V, N279K, K280, P301L, V337M, R406W) found in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). The mutant proteins were expressed on the basis of both full-length tau (htau40) and constructs derived from the repeat domain. They were analyzed with respect to the capacity to enhance microtubule assembly, binding of tau to microtubules, secondary structure content, and aggregation into Alzheimer-like paired helical or straight filaments. We find that the mutations cause a moderate decrease in microtubule interactions and stabilization, and they show no gross structural changes compared with the natively unfolded conformation of the wild-type protein, but the aggregation into PHFs is strongly enhanced, particularly for the mutants K280 and P301L. This gain of pathological aggregation would be consistent with the autosomal dominant nature of the disease.
ID 6982
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=6982
Barghorn, S., Zheng-Fischhofer, Q., Ackmann, M., Biernat, J., von Bergen, M., Mandelkow, E.-M., Mandelkow, E. (2000):
Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias
Biochemistry 39 (38), 11714 - 11721