000909156 001__ 909156
000909156 005__ 20230404101939.0
000909156 0247_ $$2doi$$a10.3389/fmolb.2022.849979
000909156 0247_ $$2Handle$$a2128/31687
000909156 0247_ $$2pmid$$a35372496
000909156 0247_ $$2WOS$$aWOS:000778672400001
000909156 037__ $$aFZJ-2022-03035
000909156 082__ $$a570
000909156 1001_ $$0P:(DE-HGF)0$$aKhemtemourian, Lucie$$b0$$eCorresponding author
000909156 245__ $$aStructural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide
000909156 260__ $$aLausanne$$bFrontiers$$c2022
000909156 3367_ $$2DRIVER$$aarticle
000909156 3367_ $$2DataCite$$aOutput Types/Journal article
000909156 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1676540288_5317
000909156 3367_ $$2BibTeX$$aARTICLE
000909156 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000909156 3367_ $$00$$2EndNote$$aJournal Article
000909156 520__ $$aThe islet amyloid polypeptide (IAPP) is the main constituent of the amyloid fibrils found in the pancreas of type 2 diabetes patients. The aggregation of IAPP is known to cause cell death, where the cell membrane plays a dual role: being a catalyst of IAPP aggregation and being the target of IAPP toxicity. Using ATR-FTIR spectroscopy, transmission electron microscopy, and molecular dynamics simulations we investigate the very first molecular steps following IAPP binding to a lipid membrane. In particular, we assess the combined effects of the charge state of amino-acid residue 18 and the IAPP-membrane interactions on the structures of monomeric and aggregated IAPP. Distinct IAPP-membrane interaction modes for the various IAPP variants are revealed. Membrane binding causes IAPP to fold into an amphipathic α-helix, which in the case of H18K-, and H18R-IAPP readily moves beyond the headgroup region. For all IAPP variants but H18E-IAPP, the membrane-bound helix is an intermediate on the way to amyloid aggregation, while H18E-IAPP remains in a stable helical conformation. The fibrillar aggregates of wild-type IAPP and H18K-IAPP are dominated by an antiparallel β-sheet conformation, while H18R- and H18A-IAPP exhibit both antiparallel and parallel β-sheets as well as amorphous aggregates. Our results emphasize the decisive role of residue 18 for the structure and membrane interaction of IAPP. This residue is thus a good therapeutic target for destabilizing membrane-bound IAPP fibrils to inhibit their toxic actions.
000909156 536__ $$0G:(DE-HGF)POF4-5241$$a5241 - Molecular Information Processing in Cellular Systems (POF4-524)$$cPOF4-524$$fPOF IV$$x0
000909156 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de
000909156 7001_ $$0P:(DE-Juel1)176262$$aFatafta, Hebah$$b1$$ufzj
000909156 7001_ $$0P:(DE-HGF)0$$aDavion, Benoit$$b2
000909156 7001_ $$0P:(DE-HGF)0$$aLecomte, Sophie$$b3
000909156 7001_ $$0P:(DE-HGF)0$$aCastano, Sabine$$b4
000909156 7001_ $$0P:(DE-Juel1)132024$$aStrodel, Birgit$$b5$$eCorresponding author$$ufzj
000909156 773__ $$0PERI:(DE-600)2814330-9$$a10.3389/fmolb.2022.849979$$gVol. 9, p. 849979$$p849979$$tFrontiers in molecular biosciences$$v9$$x2296-889X$$y2022
000909156 8564_ $$uhttps://juser.fz-juelich.de/record/909156/files/fmolb-09-849979.pdf$$yOpenAccess
000909156 8767_ $$d2022-12-27$$eAPC$$jDeposit$$z2507,50 USD
000909156 909CO $$ooai:juser.fz-juelich.de:909156$$pdnbdelivery$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire
000909156 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)176262$$aForschungszentrum Jülich$$b1$$kFZJ
000909156 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132024$$aForschungszentrum Jülich$$b5$$kFZJ
000909156 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$$x0
000909156 9141_ $$y2022
000909156 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-08-18
000909156 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2020-08-18
000909156 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000909156 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2020-08-18
000909156 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2020-08-18
000909156 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000909156 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2020-08-18
000909156 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-22
000909156 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-22
000909156 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-05-11T12:25:52Z
000909156 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-05-11T12:25:52Z
000909156 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2021-05-11T12:25:52Z
000909156 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-22
000909156 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-22
000909156 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-22
000909156 915pc $$0PC:(DE-HGF)0001$$2APC$$aLocal Funding
000909156 915pc $$0PC:(DE-HGF)0002$$2APC$$aDFG OA Publikationskosten
000909156 915pc $$0PC:(DE-HGF)0003$$2APC$$aDOAJ Journal
000909156 920__ $$lyes
000909156 9201_ $$0I:(DE-Juel1)IBI-7-20200312$$kIBI-7$$lStrukturbiochemie$$x0
000909156 980__ $$ajournal
000909156 980__ $$aVDB
000909156 980__ $$aI:(DE-Juel1)IBI-7-20200312
000909156 980__ $$aAPC
000909156 980__ $$aUNRESTRICTED
000909156 9801_ $$aAPC
000909156 9801_ $$aFullTexts