The structure of tyrosine-10 favors ionic conductance of Alzheimer’s disease-associated full-length amyloid-β channels

Abhijith G. Karkisaval, Rowan Hassan, Andrew Nguyen, Benjamin Balster, Faisal Abedin, Ratnesh Lal () and Suren A. Tatulian ()
Additional contact information
Abhijith G. Karkisaval: University of California San Diego
Rowan Hassan: University of Central Florida
Andrew Nguyen: University of California San Diego
Benjamin Balster: University of California San Diego
Faisal Abedin: University of Central Florida
Ratnesh Lal: University of California San Diego
Suren A. Tatulian: University of Central Florida

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Amyloid β (Aβ) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer’s disease. The relative roles of various Aβ isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular dichroism, FTIR and fluorescence spectroscopy to characterize channel activities of four most prevalent Aβ peptides, Aβ1-42, Aβ1-40, and their pyroglutamylated forms (AβpE3-42, AβpE3-40) and correlate them with the peptides’ structural features. Solvent-induced fluorescence splitting of tyrosine-10 is discovered and used to assess the sequestration from the solvent and membrane insertion. Aβ1-42 effectively embeds in lipid membranes, contains large fraction of β-sheet in a β-barrel-like structure, forms multi-subunit pores in membranes, and displays well-defined ion channel features. In contrast, the other peptides are partially solvent-exposed, contain minimal β-sheet structure, form less-ordered assemblies, and produce irregular ionic currents. These findings illuminate the structural basis of Aβ neurotoxicity through membrane permeabilization and may help develop therapies that target Aβ-membrane interactions.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43821-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-43821-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43821-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().