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Exploring Protein-Glycan Interactions: Advances in Nuclear Magnetic Resonance
Published on: August 26, 2025
A biophysical insight into the RANTES-glycosaminoglycan interaction
Angelika Rek1, Barbara Brandner, Elena Geretti
1ProtAffin Biotechnologie AG, Reininghausstrasse 13a, A-8020 Graz, Austria.
Biochimica Et Biophysica Acta
|May 21, 2009
Summary
Chemokines like RANTES bind to glycosaminoglycans (GAGs), promoting leukocyte activation. Heparan sulfate enhances RANTES oligomerization, crucial for its function and receptor binding.
Area of Science:
- Biochemistry
- Immunology
- Structural Biology
Background:
- Chemokine binding to glycosaminoglycans (GAGs) is essential for leukocyte recruitment and activation.
- Chemokine oligomerization is recognized as a key factor influencing GAG binding affinity and biological activity.
Purpose of the Study:
- To investigate the role of RANTES oligomerization in its interaction with GAGs.
- To elucidate the impact of heparan sulfate on RANTES oligomerization and binding kinetics.
- To determine the influence of GAG chain length on RANTES binding affinity.
Main Methods:
- Fluorescence anisotropy was used to determine the oligomerization constant of RANTES.
- Surface plasmon resonance (SPR) and thermal unfolding experiments assessed GAG-induced oligomerization and binding.
- Isothermal fluorescence titrations and Far-UV CD spectroscopy analyzed RANTES-GAG binding affinities and conformational changes.
Main Results:
- Heparan sulfate promotes RANTES oligomerization, increasing binding cooperativity and thermal stability.
- GAG-induced oligomerization of RANTES leads to cooperative binding, as evidenced by bi-phasic Scatchard plots.
- Optimal binding affinities were observed with heparin dp18 (Kd = 31.7 nM) and heparan sulfate dp14 (Kd = 42.9 nM).
- RANTES undergoes a conformational change upon heparan sulfate binding, which is critical for oligomerization and GPCR activation.
Conclusions:
- Heparan sulfate-induced oligomerization of RANTES is a critical mechanism for enhancing chemokine-GAG interactions.
- The conformational change of RANTES upon GAG binding is a prerequisite for oligomerization and subsequent receptor activation.
- Oligomerization-deficient RANTES mutants exhibit impaired GAG binding and chemotactic activity, highlighting the functional significance of this process.
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