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Thresholds and ultrasensitivity from negative cooperativity.

S H Ha1, J E Ferrell2

  • 1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.

Science (New York, N.Y.)
|May 14, 2016
PubMed
Summary
This summary is machine-generated.

Negative cooperativity in receptor binding can create highly ultrasensitive biological responses with thresholds, especially when ligands bind with high affinity. This mechanism is crucial for complex biological behaviors like bistability and oscillations.

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Molecular Biology

Background:

  • Negative cooperativity describes reduced ligand binding affinity after initial binding to multimeric receptors.
  • This phenomenon typically results in a more graded receptor response.

Purpose of the Study:

  • To investigate the impact of negative cooperativity on receptor-ligand dynamics under specific conditions.
  • To explore the potential for negative cooperativity to generate ultrasensitive biological responses.

Main Methods:

  • Theoretical modeling of receptor-ligand interactions.
  • Analysis of experimental results concerning binding affinity and ligand depletion.

Main Results:

  • Negative cooperativity, combined with high ligand affinity and significant ligand depletion, produces a highly ultrasensitive receptor response.
  • This ultrasensitivity is characterized by a pronounced threshold effect.

Conclusions:

  • Negative cooperativity can drive qualitatively different biological responses beyond simple graded changes.
  • The interplay of negative cooperativity, high affinity, and ligand depletion is critical for generating ultrasensitivity and thresholds.
  • These ultrasensitive responses are fundamental to complex biological systems, including bistability and oscillations, highlighting the importance of negative cooperativity in biological regulation.