How Human Galectins Bind to Cancer-Related Antigens
Author Information
Author(s): Bian Cheng-Feng, Zhang Ying, Sun Hui, Li De-Feng, Wang Da-Cheng
Primary Institution: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China
Hypothesis
The study investigates the distinct binding properties of human galectins Gal-1 and Gal-3 to the Thomsen-Friedenreich antigen.
Conclusion
Gal-3 binds to the Thomsen-Friedenreich antigen with significantly higher affinity than Gal-1, which has a structural hindrance preventing effective binding.
Supporting Evidence
- Gal-3 binds to the TF antigen with a dissociation constant (Kd) of 47 µM, while Gal-1 has a Kd of 4000 µM.
- Mutagenesis experiments revealed that a specific loop in Gal-1 restricts its ability to bind to the TF antigen.
- The crystal structures of Gal-3 complexed with TF antigen show a unique binding mode involving a water-mediated hydrogen bond network.
Takeaway
This study shows that two proteins, Gal-1 and Gal-3, interact differently with a sugar found in many cancer cells, which could help us understand how to target cancer better.
Methodology
The study used isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) assays to measure binding affinities and crystal structures to analyze the binding modes.
Limitations
The study primarily focuses on in vitro binding properties and may not fully represent in vivo interactions.
Digital Object Identifier (DOI)
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