FGF1 Fusions with the Fc Fragment of IgG1 for the Assembly of GFPpolygons-Mediated Multivalent Complexes Recognizing FGFRs

FGFRs are cell surface receptors that, when activated by specific FGFs ligands, transmit signals through the plasma membrane, regulating key cellular processes such as differentiation, division, motility, metabolism and death. We have recently shown that the modulation of the spatial distribution of...

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Published in:Biomolecules (Basel, Switzerland) Switzerland), 2021-07, Vol.11 (8), p.1088
Main Authors: Poźniak, Marta, Zarzycka, Weronika, Porębska, Natalia, Knapik, Agata, Marczakiewicz-Perera, Paulina, Zakrzewska, Malgorzata, Otlewski, Jacek, Opaliński, Łukasz
Format: Article
Language:English
Subjects:
Antibiotics
Antibodies
Binding sites
Biological activity
Cell culture
Cell fate
Cell surface
Endocytosis
FGF1
FGFR
Fibroblast growth factor 1
Fibroblast growth factor receptor 1
Fibroblasts
Growth factors
Immunoglobulin G
Kinases
Ligands
Oligomerization
Plasmids
Protein G
Proteins
Receptor density
signaling
Spatial distribution
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Summary:FGFRs are cell surface receptors that, when activated by specific FGFs ligands, transmit signals through the plasma membrane, regulating key cellular processes such as differentiation, division, motility, metabolism and death. We have recently shown that the modulation of the spatial distribution of FGFR1 at the cell surface constitutes an additional mechanism for fine-tuning cellular signaling. Depending on the multivalent, engineered ligand used, the clustering of FGFR1 into diverse supramolecular complexes enhances the efficiency and modifies the mechanism of receptor endocytosis, alters FGFR1 lifetime and modifies receptor signaling, ultimately determining cell fate. Here, we present a novel approach to generate multivalent FGFR1 ligands. We functionalized FGF1 for controlled oligomerization by developing N- and C-terminal fusions of FGF1 with the Fc fragment of human IgG1 (FGF1-Fc and Fc-FGF1). As oligomerization scaffolds, we employed GFPpolygons, engineered GFP variants capable of well-ordered multivalent display, fused to protein G to ensure binding of Fc fragment. The presented strategy allows efficient assembly of oligomeric FGFR1 ligands with up to twelve receptor binding sites. We show that multivalent FGFR1 ligands are biologically active and trigger receptor clustering on the cell surface. Importantly, the approach described in this study can be easily adapted to oligomerize alternative growth factors to control the activity of other cell surface receptors.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom11081088