The FGF21 Receptor Signaling Complex: Klothoβ, FGFR1c, and Other Regulatory Interactions

Area of Science:

• Endocrinology and Metabolism
• Molecular Cell Biology
• Protein Structure and Signaling

Background:

• Fibroblast Growth Factor 21 (FGF21) is an endocrine cytokine with significant metabolic effects.
• FGF21 signaling involves a complex of receptors and co-receptors, crucial for its systemic actions.
• Key components include Fibroblast Growth Factor Receptors (FGFRs) and Klotho co-receptors.

Purpose of the Study:

• To detail the structure and function of the FGF21 receptor/co-receptor signaling complex.
• To elucidate the specific interactions between FGF21, FGFR1c, and the co-receptor KLB.
• To explore regulatory mechanisms influencing FGF21 signaling complex formation and intensity.

Main Methods:

• Review of structural features of FGF ligands, FGFRs, and Klotho co-receptors.
• Focus on the specific interaction of FGF21 with FGFR1c and KLB.
• Analysis of receptor stoichiometry and regulation by other interacting molecules.

Main Results:

• Detailed structural insights into FGF21, FGFR1c, and KLB interactions.
• Characterization of the signaling complex formation at the plasma membrane.
• Exploration of how stoichiometry and regulatory interactions modulate signaling intensity.

Conclusions:

• The structure of the FGF21-FGFR1c-KLB complex dictates metabolic signaling.
• Stoichiometry and accessory interactions fine-tune FGF21's systemic effects.
• Further understanding of this complex can inform therapeutic strategies for metabolic disorders.