Stoichiometry-controlled secondary structure transition of amyloid-derived supramolecular dipeptide co-assemblies

Wei Ji, Chengqian Yuan, Priyadarshi Chakraborty, Sharon Gilead, Xuehai Yan, Ehud Gazit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Conformational transitions of secondary structures are a crucial factor in many protein misfolding diseases. However, the actual transition of folded proteins into β-sheet-rich structures is not fully understood. Inhibition of aggregate formation, mediated by the β-sheet conformation, and control of the secondary structural transition of proteins and peptides could potentially attenuate the development of amyloid-associated diseases. Here we describe a stoichiometry-controlled secondary structure transition of amyloid-derived dipeptide assemblies from a β-sheet to supramolecular helix conformation through co-assembly with a bipyridine derivative. The transition is mainly mediated by the intermolecular hydrogen bonds and π-π interactions between the two components, which induce the altered stacking and conformation of the co-assemblies, as confirmed by experimental results and computational simulations. This work not only exemplifies a feasible strategy to disrupt the β-sheet conformation, underlying amyloid-like fibril formation, but also provides a conceptual basis for the future utilization of the helical nanostructures in various biological applications.

Original languageEnglish
Article number65
JournalCommunications Chemistry
Volume2
Issue number1
DOIs
StatePublished - 1 Dec 2019

Funding

FundersFunder number
Chinese Academy ofSciences
European Union Horizon 2020 Research and Innovation Program
Innovation Research Community Science Fund21821005
National Natural Science Fund BRICS STI Framework Programme51861145304
Horizon 2020 Framework Programme694426
European Commission
National Natural Science Foundation of China21522307, 21802143

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