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Updated: Jun 8, 2026
08:58
Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques
Published on: July 5, 2018
Glycosylation stabilizes TNFα and receptor complexes: structural and biophysical implications
Karolina Sławińska1, Gabriela Całka-Kuc1, Martyna Maszota-Zieleniak2
1Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, Gdańsk, 80-308, Poland.
Carbohydrate Research
|June 6, 2026
Summary
Glycosylation enhances tumor necrosis factor alpha (TNFα) binding to its receptors TNFR1 and TNFR2. This modification increases protein stability and receptor interaction affinity, impacting cytokine signaling pathways.
Area of Science:
- Biochemistry
- Structural Biology
- Immunology
Background:
- Glycosylation is a key post-translational modification influencing protein function.
- The precise impact of glycosylation on cytokine-receptor interactions, specifically TNFα with TNFR1 and TNFR2, requires further elucidation.
Purpose of the Study:
- To investigate the mechanistic effects of TNFα glycosylation on its binding affinity and stability with TNFR1 and TNFR2.
- To elucidate the role of glycan structures in mediating TNFα-receptor complex formation and stability.
Main Methods:
- Utilized biophysical techniques including nano differential scanning fluorescence (nanoDSF) for thermal stability assessment and microscale thermophoresis (MST) for binding affinity quantification.
- Employed molecular modeling and molecular dynamics (MD) simulations to analyze the structural and energetic contributions of glycosylation to TNFα-receptor complexes.
Main Results:
- Glycosylated TNFα demonstrated enhanced thermal stability and formed more stable complexes with TNFR1 and TNFR2 compared to non-glycosylated TNFα.
- Significant increases in binding affinity were observed for glycosylated TNFα with TNFR2 (four-fold increase) and TNFR1 (detectable binding vs. undetectable for non-glycosylated).
- MD simulations revealed that glycans favorably contribute to complex stability, with effects varying by glycan length and receptor type, particularly pronounced for TNFR1.
Conclusions:
- TNFα glycosylation promotes the formation of more stable receptor complexes and enhances binding affinity through glycan-mediated stabilization effects.
- These findings provide a qualitative model for understanding how glycosylation modulates cytokine-receptor interactions and signaling outcomes.
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