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Ligand-receptor interactions: detailed evaluation of occupancy-dependent affinity
Journal of Cellular Biochemistry
|January 1, 1986
Summary
Receptor occupancy significantly impacts ligand binding affinity, shifting from high to low affinity as more receptors are occupied. This influences cell activation and may regulate ligand-induced responses.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Scatchard plot curvilinearity in binding systems is not fully understood.
- It may indicate heterogeneous receptors or negatively interacting binding sites.
- Receptor occupancy-dependent affinity requires further investigation.
Purpose of the Study:
- To investigate the effect of receptor occupancy on ligand binding affinity.
- To analyze the human lymphocyte-leukoagglutinin (LPHA) system as a model.
- To understand the relationship between occupancy, affinity, and cell activation.
Main Methods:
- Utilized the human lymphocyte-leukoagglutinin (LPHA) system.
- Calculated total binding capacity using a least-squares model.
- Analyzed receptor-ligand complex dissociation velocity across various occupancies.
Main Results:
- Receptor affinity is high (1.8 X 10^8 M^-1) at low occupancy (<0.085) and low (1.5 X 10^6 M^-1) at high occupancy (>=0.085).
- Occupancy inversely affects affinity rapidly and persistently.
- Cell activation begins at ~0.004 occupancy and is maximized at ~0.07 occupancy.
Conclusions:
- Findings support the negative cooperativity hypothesis, where occupancy influences affinity.
- Receptor occupancy plays a key role in regulating ligand-induced cellular responses.
- High occupancy leads to redundant, potentially cytotoxic binding sites.