Structural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide
| dc.rights.license | open | en_US |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | KHEMTEMOURIAN, Lucie | |
| dc.contributor.author | FATAFTA, Hebah | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | DAVION, Benoit | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | LECOMTE, Sophie | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | CASTANO, Sabine | |
| dc.contributor.author | STRODEL, Birgit | |
| dc.date.accessioned | 2024-09-20T11:51:28Z | |
| dc.date.available | 2024-09-20T11:51:28Z | |
| dc.date.issued | 2022-03-15 | |
| dc.identifier.issn | 2296-889X | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/201707 | |
| dc.description.abstractEn | 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. | |
| dc.language.iso | EN | en_US |
| dc.rights | CC0 1.0 Universal | * |
| dc.rights.uri | http://creativecommons.org/publicdomain/zero/1.0/ | * |
| dc.subject.en | Islet amyloid polypeptide | |
| dc.subject.en | Type 2 diabetes mellitus | |
| dc.subject.en | Amylin | |
| dc.subject.en | Amyloid aggregation | |
| dc.subject.en | Peptide-membrane interactions | |
| dc.title.en | Structural Dissection of the First Events Following Membrane Binding of the Islet Amyloid Polypeptide | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.3389/fmolb.2022.849979 | en_US |
| dc.subject.hal | Chimie/Matériaux | en_US |
| bordeaux.journal | Frontiers in Molecular Biosciences | en_US |
| bordeaux.volume | 9 | en_US |
| bordeaux.hal.laboratories | CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Jülich Supercomputing Centre, Forschungszentrum Jülich | en_US |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Frontiers%20in%20Molecular%20Biosciences&rft.date=2022-03-15&rft.volume=9&rft.eissn=2296-889X&rft.issn=2296-889X&rft.au=KHEMTEMOURIAN,%20Lucie&FATAFTA,%20Hebah&DAVION,%20Benoit&LECOMTE,%20Sophie&CASTANO,%20Sabine&rft.genre=article |
