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Self-Assembly of Insulin-Derived Chimeric Peptides into Two-Component Amyloid Fibrils: The Role of Coulombic Interactions

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cris.lastimport.scopus2024-02-12T20:09:35Z
dc.abstract.enCanonical amyloid fibrils are composed of covalently identical polypeptide chains. Here, we employ kinetic assays, atomic force microscopy, infrared spectroscopy, circular dichroism, and molecular dynamics simulations to study fibrillization patterns of two chimeric peptides, ACC1–13E8 and ACC1–13K8, in which a potent amyloidogenic stretch derived from the N-terminal segment of the insulin A-chain (ACC1–13) is coupled to octaglutamate or octalysine segments, respectively. While large electric charges prevent aggregation of either peptide at neutral pH, stoichiometric mixing of ACC1–13E8 and ACC1–13K8 triggers rapid self-assembly of two-component fibrils driven by favorable Coulombic interactions. The low-symmetry nonpolar ACC1–13 pilot sequence is crucial in enforcing the fibrillar structure consisting of parallel β-sheets as the self-assembly of free poly-E and poly-K chains under similar conditions results in amorphous antiparallel β-sheets. Interestingly, ACC1–13E8 forms highly ordered fibrils also when paired with nonpolypeptide polycationic amines such as branched polyethylenimine, instead of ACC1–13K8. Such synthetic polycations are more effective in triggering the fibrillization of ACC1–13E8 than poly-K (or poly-E in the case of ACC1–13K8). The high conformational flexibility of these polyamines makes up for the apparent mismatch in periodicity of charged groups. The results are discussed in the context of mechanisms of heterogeneous disease-related amyloidogenesis.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorDzwolak, Wojciech
dc.contributor.authorGuza, Marcin
dc.contributor.authorPuławski, Wojciech
dc.contributor.authorDec, Robert
dc.contributor.authorFortunka, Mateusz
dc.date.accessioned2024-01-26T07:31:07Z
dc.date.available2024-01-26T07:31:07Z
dc.date.copyright2023-07-26
dc.date.issued2023
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number30
dc.description.versionFINAL_PUBLISHED
dc.description.volume127
dc.identifier.doi10.1021/ACS.JPCB.3C00976
dc.identifier.issn1520-6106
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/119568
dc.identifier.weblinkhttps://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.3c00976
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Physical Chemistry B
dc.relation.pages6597-6607
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enLIQUID PHASE-SEPARATION
dc.subject.enALZHEIMERS-DISEASE
dc.subject.enPROTEIN
dc.subject.enPOLYMORPHISM
dc.subject.enAGGREGATION
dc.subject.enPATHWAY
dc.subject.enAMBER
dc.subject.enSTATE
dc.titleSelf-Assembly of Insulin-Derived Chimeric Peptides into Two-Component Amyloid Fibrils: The Role of Coulombic Interactions
dc.typeJournalArticle
dspace.entity.typePublication