De novo developed protein binders mimicking Interferon lambda signaling

Lucie Kolářová, Jiří Zahradník, Maroš Huličiak, Pavel Mikulecký, Yoav Peleg, Maya Shemesh, Gideon Schreiber, Bohdan Schneider

Research output: Contribution to journalArticlepeer-review

Abstract

We hereby describe the process of design and selection of nonantibody protein binders mimicking cytokine signaling. We chose to mimic signaling of IFN-λ1, type 3 interferon (also known as IL-29) for its novelty and the importance of its biological functions. All four known interferons λ signal through binding to the extracellular domains of IL-28 receptor 1 (IL-28R1) and IL-10 receptor 2 (IL-10R2). Our binders were therefore trained to bind both receptors simultaneously. The bifunctional binder molecules were developed by yeast display, a method of directed evolution. The signaling capacity of the bivalent binders was tested by measuring phosphorylation of the JAK/STAT signaling pathway and production of mRNA of six selected genes naturally induced by IFN- λ1 in human cell lines. The newly developed bivalent binders offer opportunities to study cytokine-related biological functions and modulation of the cell behavior by receptor activation on the cell surfaces alternative to the use of natural IFN-λ.
Original languageEnglish
Pages (from-to)2672-2684
Number of pages13
JournalThe Febs Journal
Volume289
Issue number9
DOIs
StatePublished Online - 26 Nov 2021

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