The influence of the Δk280 mutation and N- or C-terminal extensions on the structure, dynamics, and fibril morphology of the tau R2 repeat

dc.bibliographicCitation.firstPage7710eng
dc.bibliographicCitation.issue17eng
dc.bibliographicCitation.journalTitlePhysical Chemistry Chemical Physicseng
dc.bibliographicCitation.volume16eng
dc.contributor.authorRaz, Y.
dc.contributor.authorAdler, J.
dc.contributor.authorVogel, A.
dc.contributor.authorScheidt, H.A.
dc.contributor.authorHäupl, T.
dc.contributor.authorAbel, B.
dc.contributor.authorHuster, D.
dc.contributor.authorMiller, Y.
dc.date.accessioned2020-11-12T07:21:56Z
dc.date.available2020-11-12T07:21:56Z
dc.date.issued2014
dc.description.abstractTau is a microtubule-associated protein and is involved in microtubule assembly and stabilization. It consists of four repeats that bind to the microtubule. The ΔK280 deletion mutation in the tau R2 repeat region is directly associated with the development of the frontotemporal dementia parkinsonism linked to chromosome 17 (FTDP-17). This deletion mutation is known to accelerate tau R2 repeat aggregation. However, the secondary and the tertiary structures of the self-assembled ΔK280 tau R2 repeat mutant aggregates are still controversial. Moreover, it is unclear whether extensions by one residue in the N- or the C-terminus of this mutant can influence the secondary or the tertiary structure. Herein, we combine solid-state NMR, atomic force microscopy, electron microscopy and all-atom explicit molecular dynamics simulations to investigate the effects of the deletion mutation and the N- and the C-terminal extension of this mutant on the structure. Our main findings show that the deletion mutation induces the formation of small aggregates, such as oligomers, and reduces the formation of fibrils. However, the extensions in the N- or the C-terminus revealed more fibril formation than small aggregates. Further, in the deletion mutation only one structure is preferred, while the N- and the C-terminal extensions strongly lead to polymorphic states. Finally, our broad and combined experimental and computational techniques provide direct structural information regarding ΔK280 tau R2 repeat mutant aggregates and their extensions in the N- and C-terminii by one residue.eng
dc.description.versionpublishedVersioneng
dc.identifier.urihttps://doi.org/10.34657/4513
dc.identifier.urihttps://oa.tib.eu/renate/handle/123456789/5884
dc.language.isoengeng
dc.publisherLondon [u.a.] : Royal Society of Chemistryeng
dc.relation.doihttps://doi.org/10.1039/c3cp54890b
dc.relation.issn1463-9076
dc.rights.licenseCC BY-NC 3.0 Unportedeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/eng
dc.subject.ddc540eng
dc.subject.otherprotein aggregateeng
dc.subject.othertau proteineng
dc.subject.otheramino acid sequenceeng
dc.subject.otherchemistryeng
dc.subject.otherfrontotemporal dementiaeng
dc.subject.othergene deletioneng
dc.subject.othergeneticseng
dc.subject.otherhumaneng
dc.subject.othermolecular dynamicseng
dc.subject.othermolecular geneticseng
dc.subject.otherprotein conformationeng
dc.subject.otherultrastructureeng
dc.subject.otherAmino Acid Sequenceeng
dc.subject.otherFrontotemporal Dementiaeng
dc.subject.otherHumanseng
dc.subject.otherMolecular Dynamics Simulationeng
dc.subject.otherMolecular Sequence Dataeng
dc.subject.otherProtein Aggregateseng
dc.subject.otherProtein Conformationeng
dc.subject.otherSequence Deletioneng
dc.subject.othertau Proteinseng
dc.titleThe influence of the Δk280 mutation and N- or C-terminal extensions on the structure, dynamics, and fibril morphology of the tau R2 repeateng
dc.typeArticleeng
dc.typeTexteng
tib.accessRightsopenAccesseng
wgl.contributorIOMeng
wgl.subjectChemieeng
wgl.typeZeitschriftenartikeleng
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Raz2014.pdf
Size:
3.16 MB
Format:
Adobe Portable Document Format
Description:
Collections