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

0574534 - BTÚ 2024 RIV CH eng J - Journal Article
Pham, Phuong Ngoc - Zahradník, J. - Kolářová, Lucie - Schneider, Bohdan - Fuertes, Gustavo
Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light.
Frontiers in molecular biosciences. Roč. 10, JUL 7 2023 (2023), č. článku 1214235. E-ISSN 2296-889X
R&D Projects: GA MŠMT LM2023042; GA MŠMT EF15_003/0000447; GA MŠMT(CZ) EF18_046/0015974; GA MŠMT LX22NPO5102
Institutional support: RVO:86652036
Keywords : protein-protein interactions (PPI) * interleukin-24 * cytokines * optobinders * genetically encoded non-canonical amino acids (ncAA) * photocaged proteins
OECD category: Biochemistry and molecular biology
Impact factor: 5, year: 2022
Method of publishing: Open access
https://www.frontiersin.org/articles/10.3389/fmolb.2023.1214235/full

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.
Permanent Link: https://hdl.handle.net/11104/0345655