Related Experiment Video

Updated: Mar 21, 2026

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
10:28

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

Published on: August 17, 2019

10.6K

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

Insights

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.

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.

More Related Videos

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

9.0K
Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry13:26

Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry

Published on: September 13, 2014

63.0K

Related Concept Videos

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
9.3K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

2.8K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

3.2K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.5K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

2.7K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.8K