Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light

Autor: Phuong Ngoc Pham, Jiří Zahradník, Lucie Kolářová, Bohdan Schneider, Gustavo Fuertes
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Molecular Biosciences, Vol 10 (2023)
Druh dokumentu: article
ISSN: 2296-889X
DOI: 10.3389/fmolb.2023.1214235
Popis: Human interleukin 24 (IL-24) is a multifunctional cytokine that represents an important target for autoimmune diseases and cancer. Since the biological functions of IL-24 depend on interactions with membrane receptors, on-demand regulation of the affinity between IL-24 and its cognate partners offers exciting possibilities in basic research and may have applications in therapy. As a proof-of-concept, we developed a strategy based on recombinant soluble protein variants and genetic code expansion technology to photocontrol the binding between IL-24 and one of its receptors, IL-20R2. Screening of non-canonical ortho-nitrobenzyl-tyrosine (NBY) residues introduced at several positions in both partners was done by a combination of biophysical and cell signaling assays. We identified one position for installing NBY, tyrosine70 of IL-20R2, which results in clear impairment of heterocomplex assembly in the dark. Irradiation with 365-nm light leads to decaging and reconstitutes the native tyrosine of the receptor that can then associate with IL-24. Photocaged IL-20R2 may be useful for the spatiotemporal control of the JAK/STAT phosphorylation cascade.
Databáze: Directory of Open Access Journals