Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Forced amyloidogenic cooperativity of structurally incompatible peptide segments: Fibrillization behavior of highly aggregation-prone A-chain fragment of insulin coupled to all-L, and alternating L/D octaglutamates

Uproszczony widok
dc.abstract.enAggregation of proteins into amyloid fibrils is driven by interactions between relatively small amyloidogenic segments. The interplay between aggregation-prone and aggregation-resistant fragments within a single polypeptide chain remains obscure. Here, we examine fibrillization behavior of two chimeric peptides, ACC1–13E8 and ACC1–13E8(L/D), in which the highly amyloidogenic fragment of insulin (ACC1–13) is extended by an octaglutamate segment composed of all-L (E8), or alternating L/D residues (E8(L/D)). As separate entities, ACC1–13 readily forms fibrils with the infrared features of parallel β-sheet while E8 forms antiparallel β-sheets with the distinct infrared characteristics. This contrasts with the profoundly aggregation-resistant E8(L/D), although L/D patterns have been hypothesized as compatible with aggregated α-sheets. ACC1–13E8 and ACC1–13E8(L/D) are found to be equally prone to fibrillization at low pH, or in the presence of Ca2+ ions. Fibrillar states of both ACC1–13E8 and ACC1–13E8(L/D) reveal the infrared features of highly ordered parallel β-sheet without evidence of β2-aggregates (ACC1–13E8) or α-sheets (ACC1–13E8(L/D)). Hence, the preferred structural pattern of ACC1–13 overrides the tendency of E8 to form antiparallel β-sheets and enforces the fibrillar order in E8(L/D). We demonstrate how the powerful amyloid stretch determines the overall amyloid structure forcing non-amyloidogenic fragments to participate in its native amyloid pattern.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorDzwolak, Wojciech
dc.contributor.authorWacławska, Matylda
dc.contributor.authorPuławski, Wojciech
dc.contributor.authorOkoń, Róża
dc.contributor.authorDec, Robert
dc.date.accessioned2024-01-25T01:14:15Z
dc.date.available2024-01-25T01:14:15Z
dc.date.issued2022
dc.description.financePublikacja bezkosztowa
dc.description.volume223
dc.identifier.doi10.1016/J.IJBIOMAC.2022.11.050
dc.identifier.issn0141-8130
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/107335
dc.identifier.weblinkhttps://api.elsevier.com/content/article/PII:S0141813022026083?httpAccept=text/xml
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofInternational Journal of Biological Macromolecules
dc.relation.pages362-369
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enAmyloid stretch
dc.subject.enChimeric peptide
dc.subject.enHomopolypeptide
dc.titleForced amyloidogenic cooperativity of structurally incompatible peptide segments: Fibrillization behavior of highly aggregation-prone A-chain fragment of insulin coupled to all-L, and alternating L/D octaglutamates
dc.typeJournalArticle
dspace.entity.typePublication