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dc.contributor.authorWilliams, Danielle M
dc.contributor.authorThorn, David C
dc.contributor.authorDobson, Christopher M
dc.contributor.authorMeehan, Sarah
dc.contributor.authorJackson, Sophie E
dc.contributor.authorWoodcock, Joanna M
dc.contributor.authorCarver, John A
dc.date.accessioned2022-01-06T11:50:35Z
dc.date.available2022-01-06T11:50:35Z
dc.date.issued2021-10-11
dc.identifier.citationMolecules (Basel, Switzerland), volume 26, issue 20
dc.identifier.issn1420-3049
dc.identifier.otherPMC8538830
dc.identifier.other34684701
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332155
dc.description.abstract14-3-3 proteins are abundant, intramolecular proteins that play a pivotal role in cellular signal transduction by interacting with phosphorylated ligands. In addition, they are molecular chaperones that prevent protein unfolding and aggregation under cellular stress conditions in a similar manner to the unrelated small heat-shock proteins. In vivo, amyloid β (Aβ) and α-synuclein (α-syn) form amyloid fibrils in Alzheimer's and Parkinson's diseases, respectively, a process that is intimately linked to the diseases' progression. The 14-3-3ζ isoform potently inhibited in vitro fibril formation of the 40-amino acid form of Aβ (Aβ40) but had little effect on α-syn aggregation. Solution-phase NMR spectroscopy of 15N-labeled Aβ40 and A53T α-syn determined that unlabeled 14-3-3ζ interacted preferentially with hydrophobic regions of Aβ40 (L11-H21 and G29-V40) and α-syn (V3-K10 and V40-K60). In both proteins, these regions adopt β-strands within the core of the amyloid fibrils prepared in vitro as well as those isolated from the inclusions of diseased individuals. The interaction with 14-3-3ζ is transient and occurs at the early stages of the fibrillar aggregation pathway to maintain the native, monomeric, and unfolded structure of Aβ40 and α-syn. The N-terminal regions of α-syn interacting with 14-3-3ζ correspond with those that interact with other molecular chaperones as monitored by in-cell NMR spectroscopy.
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1420-3049
dc.sourcenlmid: 100964009
dc.subjectMolecular chaperone
dc.subjectα-synuclein
dc.subjectNmr Spectroscopy
dc.subjectAmyloid Fibril
dc.subjectAmyloid Β
dc.subject14-3-3 Proteins
dc.titleThe Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ.
dc.typeArticle
dc.date.updated2022-01-06T11:50:35Z
prism.publicationNameMolecules
dc.identifier.doi10.17863/CAM.79601
dcterms.dateAccepted2021-10-03
rioxxterms.versionofrecord10.3390/molecules26206120
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidThorn, David C [0000-0002-7332-2292]
dc.contributor.orcidMeehan, Sarah [0000-0002-2778-4373]
dc.contributor.orcidWoodcock, Joanna M [0000-0001-5127-9687]
dc.contributor.orcidCarver, John A [0000-0002-2441-8108]
dc.identifier.eissn1420-3049
pubs.funder-project-idNational Health and Medical Research Council (1068087)
cam.issuedOnline2021-10-11


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International