Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Ultrafast Time-Resolved Studies on Fluorescein for Recognition Strands Architecture in Amyloid Fibrils

Uproszczony widok
cris.lastimport.scopus2024-02-12T19:53:46Z
dc.abstract.enProtein aggregation is associated with numerous devastating diseases such as Alzheimer’s, Parkinson’s, and prion diseases. Development of therapeutics would benefit from knowledge of the structural organization of protein molecules in these amyloid aggregates, particularly in their aqueous biological milieu. However, detailed structural studies to date have been mainly on the solid state and have required large quantities of purified aggregate. Moreover, these conventional methods require the aggregated assembly to remain structurally stable over days or weeks required to perform the experiment, whereas the pathologically relevant species of in vivo aggregates may be shorter lived. Here, we show the organization of protein chains in dissolved amyloid aggregates can be readily determined spectroscopically using minute quantities of fluorescein-labeled protein segments in a matter of minutes. Specifically, we investigated the possibility of using the ultrafast dynamics of fluorescein to distinguish among three categories of β-sheet geometry: (1) antiparallel in-register, (2) parallel in-register, or (3) antiparallel out-of-register. Fluorescein, the most commonly used staining dye in biology and medicine, was covalently attached to the N-termini of peptide sequences selected from a library of known amyloid crystal structures. We investigated the aggregates in solution using steady-state and time-resolved absorption and fluorescence spectroscopy. We found that the dynamics of fluorescein relaxation from the excited state revealed amyloid structure-specific information. Particularly, the nonfluorescent cation form of fluorescein showed remarkable sensitivity to local environments created during aggregation. We demonstrate that time-resolved absorption is capable of differentiating strand organization in β-sheet aggregates when strong intermolecular coupling between chromophores occurs. This approach can be useful in optical recognition of specific fibril architectures of amyloid aggregates.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorEisenberg, David
dc.contributor.authorSawaya, Michael R.
dc.contributor.authorHeeger, Alan
dc.contributor.authorMikhailovsky, Alexander
dc.contributor.authorBoyer, David R.
dc.contributor.authorHańczyc, Piotr
dc.date.accessioned2024-01-26T11:18:07Z
dc.date.available2024-01-26T11:18:07Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number1
dc.description.volume122
dc.identifier.doi10.1021/ACS.JPCB.7B07923
dc.identifier.issn1520-6106
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/124093
dc.identifier.weblinkhttps://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.7b07923
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofJournal of Physical Chemistry B
dc.relation.pages8-18
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleUltrafast Time-Resolved Studies on Fluorescein for Recognition Strands Architecture in Amyloid Fibrils
dc.typeJournalArticle
dspace.entity.typePublication