001015354 001__ 1015354
001015354 005__ 20231027114416.0
001015354 0247_ $$2doi$$a10.1021/jacs.3c03980
001015354 0247_ $$2ISSN$$a0002-7863
001015354 0247_ $$2ISSN$$a1520-5126
001015354 0247_ $$2ISSN$$a1943-2984
001015354 0247_ $$2datacite_doi$$a10.34734/FZJ-2023-03674
001015354 0247_ $$2pmid$$a37555670
001015354 0247_ $$2WOS$$aWOS:001044984100001
001015354 037__ $$aFZJ-2023-03674
001015354 082__ $$a540
001015354 1001_ $$0P:(DE-Juel1)180535$$aKhaled, Mohammed$$b0$$ufzj
001015354 245__ $$aA Hairpin Motif in the Amyloid-β Peptide Is Important for Formation of Disease-Related Oligomers
001015354 260__ $$aWashington, DC$$bACS Publications$$c2023
001015354 3367_ $$2DRIVER$$aarticle
001015354 3367_ $$2DataCite$$aOutput Types/Journal article
001015354 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1695972732_21433
001015354 3367_ $$2BibTeX$$aARTICLE
001015354 3367_ $$2ORCID$$aJOURNAL_ARTICLE
001015354 3367_ $$00$$2EndNote$$aJournal Article
001015354 520__ $$aThe amyloid-β (Aβ) peptide is associated with the development of Alzheimer’s disease and is known to form highly neurotoxic prefibrillar oligomeric aggregates, which are difficult to study due to their transient, low-abundance, and heterogeneous nature. To obtain high-resolution information about oligomer structure and dynamics as well as relative populations of assembly states, we here employ a combination of native ion mobility mass spectrometry and molecular dynamics simulations. We find that the formation of Aβ oligomers is dependent on the presence of a specific β-hairpin motif in the peptide sequence. Oligomers initially grow spherically but start to form extended linear aggregates at oligomeric states larger than those of the tetramer. The population of the extended oligomers could be notably increased by introducing an intramolecular disulfide bond, which prearranges the peptide in the hairpin conformation, thereby promoting oligomeric structures but preventing conversion into mature fibrils. Conversely, truncating one of the β-strand-forming segments of Aβ decreased the hairpin propensity of the peptide and thus decreased the oligomer population, removed the formation of extended oligomers entirely, and decreased the aggregation propensity of the peptide. We thus propose that the observed extended oligomer state is related to the formation of an antiparallel sheet state, which then nucleates into the amyloid state. These studies provide increased mechanistic understanding of the earliest steps in Aβ aggregation and suggest that inhibition of Aβ folding into the hairpin conformation could be a viable strategy for reducing the amount of toxic oligomers.
001015354 536__ $$0G:(DE-HGF)POF4-5241$$a5241 - Molecular Information Processing in Cellular Systems (POF4-524)$$cPOF4-524$$fPOF IV$$x0
001015354 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de
001015354 7001_ $$0P:(DE-HGF)0$$aRönnbäck, Isabel$$b1
001015354 7001_ $$0P:(DE-HGF)0$$aIlag, Leopold L.$$b2
001015354 7001_ $$0P:(DE-HGF)0$$aGräslund, Astrid$$b3
001015354 7001_ $$0P:(DE-Juel1)132024$$aStrodel, Birgit$$b4$$eCorresponding author
001015354 7001_ $$00000-0003-0905-7911$$aÖsterlund, Nicklas$$b5$$eCorresponding author
001015354 773__ $$0PERI:(DE-600)1472210-0$$a10.1021/jacs.3c03980$$gVol. 145, no. 33, p. 18340 - 18354$$n33$$p18340 - 18354$$tJournal of the American Chemical Society$$v145$$x0002-7863$$y2023
001015354 8564_ $$uhttps://juser.fz-juelich.de/record/1015354/files/jacs.3c03980.pdf$$yOpenAccess
001015354 909CO $$ooai:juser.fz-juelich.de:1015354$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
001015354 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)180535$$aForschungszentrum Jülich$$b0$$kFZJ
001015354 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132024$$aForschungszentrum Jülich$$b4$$kFZJ
001015354 9131_ $$0G:(DE-HGF)POF4-524$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5241$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vMolecular and Cellular Information Processing$$x0
001015354 9141_ $$y2023
001015354 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-09
001015354 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2022-11-09
001015354 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-09
001015354 915__ $$0StatID:(DE-HGF)1210$$2StatID$$aDBCoverage$$bIndex Chemicus$$d2022-11-09
001015354 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
001015354 915__ $$0StatID:(DE-HGF)1200$$2StatID$$aDBCoverage$$bChemical Reactions$$d2022-11-09
001015354 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
001015354 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2023-10-21$$wger
001015354 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ AM CHEM SOC : 2022$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2023-10-21
001015354 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bJ AM CHEM SOC : 2022$$d2023-10-21
001015354 920__ $$lyes
001015354 9201_ $$0I:(DE-Juel1)IBI-7-20200312$$kIBI-7$$lStrukturbiochemie$$x0
001015354 980__ $$ajournal
001015354 980__ $$aVDB
001015354 980__ $$aUNRESTRICTED
001015354 980__ $$aI:(DE-Juel1)IBI-7-20200312
001015354 9801_ $$aFullTexts