Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias.

Content Provider	Semantic Scholar
Author	Barghorn, Stefan Zheng-Fischhöfer, Qingyi Ackmann, Michael Biernat, Jacek Bergen, Martin Von Mandelkow, Eckhard
Copyright Year	2000
Abstract	We have studied biochemical and structural parameters of several missense and deletion mutants of tau protein (G272V, N279K, DeltaK280, 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 DeltaK280 and P301L. This gain of pathological aggregation would be consistent with the autosomal dominant nature of the disease.
Starting Page	S289
Ending Page	S290
Page Count	2
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.mpasmb-hamburg.mpg.de/mand-pdf/barghorn_00.pdf
PubMed reference number	10995239v1
Volume Number	39
Issue Number	38
Journal	Biochemistry
Language	English
Access Restriction	Open
Subject Keyword	Autosomal dominant inheritance Chromosomes, Human, Pair 17 Cytoskeletal Filaments Deletion Mutation Frontotemporal dementia Microtubule Polymerization Process Microtubules Parkinsonian Disorders mutant paired helical filament
Content Type	Text
Resource Type	Article