Related Experiment Video
Updated: Jul 3, 2026
08:34
Precise Visualization of Insulin Receptors A and B in Murine Brain with an RNA In Situ Hybridization Assay
Published on: July 15, 2025
The insulin receptor: a prototype for dimeric, allosteric membrane receptors?
1Receptor Systems Biology Laboratory, Hagedorn Research Institute, Niels Steensens Vej 6, Gentofte, Denmark. pdm@novonordisk.com
Trends in Biochemical Sciences
|July 22, 2008
Summary
The insulin receptor
Area of Science:
- Biochemistry and structural biology
- Molecular and cellular signaling
Background:
- Decades of speculation on insulin receptor (IR) binding and negative cooperativity.
- Recent crystallographic structure provides new insights into IR function.
Purpose of the Study:
- To elucidate the mechanism of insulin-receptor binding and negative cooperativity.
- To compare IR mechanisms with other receptor families.
Main Methods:
- Crystallography of the insulin receptor extracellular domain.
- Kinetic analysis of receptor-ligand interactions.
Main Results:
- The study supports a bivalent crosslinking model for insulin-receptor binding.
- Receptor dimerization is a common feature across receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs).
Conclusions:
- The bivalent crosslinking model explains insulin-receptor binding and negative cooperativity.
- Similar allosteric mechanisms, including dimerization and negative cooperativity, are observed in GPCRs, akin to the IR.
Related Concept Videos
01:28Insulin: The Receptor and Signaling Pathways
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
01:58Cooperative 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...
01:58Cooperative 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...
01:30Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...
01:30Spare Receptors
Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include: