2004
DOI: 10.1021/bi048953n
|View full text |Cite
|
Sign up to set email alerts
|

Residual Structure in the Repeat Domain of Tau:  Echoes of Microtubule Binding and Paired Helical Filament Formation

Abstract: The microtubule-associated protein tau is found aggregated into paired helical filaments in the intraneuronal neurofibrillary tangle deposits of victims of Alzheimer's disease (AD) and other related dementias. Tau contains a repeat domain consisting of three or four 31-32-residue imperfect repeats that forms the core of tau filaments and is capable of self-assembling into filaments in vitro. We have used high-resolution NMR spectroscopy to characterize the structural properties of the three-repeat domain of ta… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

11
126
1

Year Published

2005
2005
2023
2023

Publication Types

Select...
9

Relationship

0
9

Authors

Journals

citations
Cited by 108 publications
(138 citation statements)
references
References 75 publications
11
126
1
Order By: Relevance
“…No ␣-helical structure was detected in the repeat domain in this study. This is contrary to other NMR studies of Tau-derived fragments that were performed, however, in the presence of helix-inducing agents such as trifluoroethanol or SDS (37)(38)(39). In addition, no strong tendency to populate ␣-helical or ␤-structure was detected in the regions flanking the repeat domain.…”
Section: Discussioncontrasting
confidence: 96%
“…No ␣-helical structure was detected in the repeat domain in this study. This is contrary to other NMR studies of Tau-derived fragments that were performed, however, in the presence of helix-inducing agents such as trifluoroethanol or SDS (37)(38)(39). In addition, no strong tendency to populate ␣-helical or ␤-structure was detected in the regions flanking the repeat domain.…”
Section: Discussioncontrasting
confidence: 96%
“…While this manuscript was in preparation an NMR study of K19 was published (26). Similar to our results, these authors observed a tendency to form ␤-structure in the beginning of R3.…”
Section: Discussionsupporting
confidence: 86%
“…In addition, as only K19 was studied, neither the structural properties of R2 nor any isoform-specific differences between three-and four-repeat tau could be addressed. Most strikingly, however, Eliezer et al (26) concluded that much of K19, comprising residues 253-267, 315-328, and 346 -361, preferentially populates helical conformations. This conclusion was based mainly on long stretches of positive C ␣ secondary chemical shifts.…”
Section: Discussionmentioning
confidence: 99%
“…The same group initially pointed out the importance of antiparallel tau dimer formation under oxidative conditions for efficient PHF assembly (Friedhoff et al, 1998b), but this prerequisite of polymerization has been recently contested (Kuret et al, 2005). Remarkably, no change in disordered molecular state of tau after dimerization was proven (Skrabana et al, 2004a;Eliezer et al, 2005;von Bergen et al, 2005). N-and C-terminal truncations of tau greatly enhanced the filament formation under oxidative conditions.…”
Section: Phf Assembly In Vitromentioning
confidence: 99%