PMID- 10995239
OWN - NLM
STAT- MEDLINE
DCOM- 20001107
LR  - 20191210
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 39
IP  - 38
DP  - 2000 Sep 26
TI  - Structure, microtubule interactions, and paired helical filament aggregation by 
      tau mutants of frontotemporal dementias.
PG  - 11714-21
AB  - 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.
FAU - Barghorn, S
AU  - Barghorn S
AD  - Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Notkestrasse 85, 
      D-22607 Hamburg, Germany.
FAU - Zheng-Fischhofer, Q
AU  - Zheng-Fischhofer Q
FAU - Ackmann, M
AU  - Ackmann M
FAU - Biernat, J
AU  - Biernat J
FAU - von Bergen, M
AU  - von Bergen M
FAU - Mandelkow, E M
AU  - Mandelkow EM
FAU - Mandelkow, E
AU  - Mandelkow E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Benzothiazoles)
RN  - 0 (Thiazoles)
RN  - 0 (tau Proteins)
RN  - 2390-54-7 (thioflavin T)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Actin Cytoskeleton/chemistry/genetics/*metabolism/ultrastructure
MH  - Benzothiazoles
MH  - Circular Dichroism
MH  - Dementia/*genetics/*metabolism/pathology
MH  - Humans
MH  - Microscopy, Electron
MH  - Microtubules/chemistry/genetics/*metabolism/ultrastructure
MH  - Mutagenesis, Site-Directed
MH  - *Mutation
MH  - Mutation, Missense
MH  - Neuropil Threads/genetics/metabolism/ultrastructure
MH  - Paclitaxel/chemistry
MH  - Protein Binding/genetics
MH  - Protein Structure, Secondary/genetics
MH  - Scattering, Radiation
MH  - Sequence Deletion
MH  - Spectrometry, Fluorescence
MH  - Thiazoles/chemistry
MH  - tau Proteins/*chemistry/*genetics/metabolism/ultrastructure
EDAT- 2000/09/20 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/20 11:00
PHST- 2000/09/20 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/20 11:00 [entrez]
AID - bi000850r [pii]
AID - 10.1021/bi000850r [doi]
PST - ppublish
SO  - Biochemistry. 2000 Sep 26;39(38):11714-21. doi: 10.1021/bi000850r.