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A Hydroponic Co-cultivation System for Simultaneous and Systematic Analysis of Plant/Microbe Molecular Interactions and Signaling
Published on: July 22, 2017
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A systematic dissection of sequence elements determining β-Klotho and FGF interaction and signaling
Sally Yu Shi1, Ya-Wen Lu1, Jason Richardson2
1Department of Cardiometabolic Disorders, Amgen Discovery Research, Amgen Inc., 1120 Veterans Blvd., South San Francisco, CA, 94080, USA.
Scientific Reports
|July 25, 2018
Summary
Endocrine fibroblast growth factors (FGFs) use β-Klotho co-receptors to activate signaling. This study identifies shared binding sites on β-Klotho and FGF19/FGF21 for metabolic regulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Endocrine fibroblast growth factors (FGFs) necessitate Klotho co-receptors for FGF receptor (FGFR) signaling.
- FGF19 and FGF21, acting via β-Klotho, are crucial regulators of glucose and lipid metabolism.
Purpose of the Study:
- To elucidate the interaction mechanisms between FGF19/FGF21 and the β-Klotho co-receptor.
- To identify specific protein regions involved in FGF-β-Klotho-FGFR signal transduction.
Main Methods:
- Hydrogen deuterium exchange coupled to mass spectrometry (HDX-MS) to map protein interaction sites.
- Alanine and arginine mutagenesis to probe residue contributions.
- Biochemical and cell-based signaling assays using full-length proteins.
Main Results:
- Identified specific interaction regions on β-Klotho and FGF19/FGF21.
- Demonstrated that both KL1 and KL2 domains of β-Klotho bind FGF19 and FGF21.
- Confirmed conserved C-terminal regions of FGF19/FGF21 mediate co-receptor interaction.
Conclusions:
- β-Klotho's KL1 and KL2 domains share binding sites for FGF19 and FGF21.
- Specific C-terminal regions of FGF19/FGF21 are critical for β-Klotho interaction.
- Findings provide mechanistic insight into endocrine FGF signaling pathways.
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