Home > Publications database > Structural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide > print

001     909156
005     20230404101939.0
024 7 _ |a 10.3389/fmolb.2022.849979
|2 doi
024 7 _ |a 2128/31687
|2 Handle
024 7 _ |a 35372496
|2 pmid
024 7 _ |a WOS:000778672400001
|2 WOS
037 _ _ |a FZJ-2022-03035
082 _ _ |a 570
100 1 _ |a Khemtemourian, Lucie
|0 P:(DE-HGF)0
|b 0
|e Corresponding author
245 _ _ |a Structural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide
260 _ _ |a Lausanne
|c 2022
|b Frontiers
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1676540288_5317
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a The 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.
536 _ _ |a 5241 - Molecular Information Processing in Cellular Systems (POF4-524)
|0 G:(DE-HGF)POF4-5241
|c POF4-524
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, Journals: juser.fz-juelich.de
700 1 _ |a Fatafta, Hebah
|0 P:(DE-Juel1)176262
|b 1
|u fzj
700 1 _ |a Davion, Benoit
|0 P:(DE-HGF)0
|b 2
700 1 _ |a Lecomte, Sophie
|0 P:(DE-HGF)0
|b 3
700 1 _ |a Castano, Sabine
|0 P:(DE-HGF)0
|b 4
700 1 _ |a Strodel, Birgit
|0 P:(DE-Juel1)132024
|b 5
|e Corresponding author
|u fzj
773 _ _ |a 10.3389/fmolb.2022.849979
|g Vol. 9, p. 849979
|0 PERI:(DE-600)2814330-9
|p 849979
|t Frontiers in molecular biosciences
|v 9
|y 2022
|x 2296-889X
856 4 _ |u https://juser.fz-juelich.de/record/909156/files/fmolb-09-849979.pdf
|y OpenAccess
909 C O |o oai:juser.fz-juelich.de:909156
|p openaire
|p open_access
|p OpenAPC
|p driver
|p VDB
|p openCost
|p dnbdelivery
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 1
|6 P:(DE-Juel1)176262
910 1 _ |a Forschungszentrum Jülich
|0 I:(DE-588b)5008462-8
|k FZJ
|b 5
|6 P:(DE-Juel1)132024
913 1 _ |a DE-HGF
|b Key Technologies
|l Natural, Artificial and Cognitive Information Processing
|1 G:(DE-HGF)POF4-520
|0 G:(DE-HGF)POF4-524
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-500
|4 G:(DE-HGF)POF
|v Molecular and Cellular Information Processing
|9 G:(DE-HGF)POF4-5241
|x 0
914 1 _ |y 2022
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2020-08-18
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2020-08-18
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2020-08-18
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2020-08-18
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2020-08-18
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2022-11-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2022-11-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2021-05-11T12:25:52Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2021-05-11T12:25:52Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Blind peer review
|d 2021-05-11T12:25:52Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2022-11-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2022-11-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2022-11-22
915 p c |a Local Funding
|2 APC
|0 PC:(DE-HGF)0001
915 p c |a DFG OA Publikationskosten
|2 APC
|0 PC:(DE-HGF)0002
915 p c |a DOAJ Journal
|2 APC
|0 PC:(DE-HGF)0003
920 _ _ |l yes
920 1 _ |0 I:(DE-Juel1)IBI-7-20200312
|k IBI-7
|l Strukturbiochemie
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-Juel1)IBI-7-20200312
980 _ _ |a APC
980 _ _ |a UNRESTRICTED
980 1 _ |a APC
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21