Related Experiment Video
Updated: Jul 10, 2026
09:40
Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
Published on: September 28, 2018
An allosteric intramolecular PDZ-PDZ interaction modulates PTP-BL PDZ2 binding specificity
Lieke C J van den Berk1, Elena Landi, Tine Walma
1Department of Cell Biology, Radboud University Nijmegen Medical Centre, The Netherlands.
Biochemistry
|November 6, 2007
Summary
PDZ domains bind protein targets. Researchers found that PDZ1 allosterically modulates PDZ2 binding preference in PTP-BL, revealing how protein context impacts PDZ domain specificity.
Area of Science:
- Molecular biology
- Protein structure and function
Background:
- PDZ domains are crucial protein interaction modules recognizing protein C-terminal motifs.
- Understanding PDZ domain binding specificity is key to deciphering cellular interaction networks.
Purpose of the Study:
- To investigate the binding preferences of the five PDZ domains within the protein tyrosine phosphatase PTP-BL.
- To elucidate the mechanism by which PDZ domain interactions are regulated.
Main Methods:
- Utilized a random C-terminal peptide lambda phage display library to screen PDZ domain binding preferences.
- Employed structural studies to determine the interaction interface between PDZ1 and PDZ2.
Main Results:
- Determined the specific binding preferences for the five PDZ domains of PTP-BL.
- Discovered that PDZ1 directly interacts with PDZ2, altering PDZ2's ligand binding specificity.
- Identified long-range allosteric effects mediated by PDZ1 on the PDZ2 peptide binding groove.
Conclusions:
- The molecular context and domain embedding significantly influence PDZ domain ligand binding specificity.
- Allosteric regulation by adjacent domains is a critical mechanism for modulating PDZ domain function.
More Related Videos
Related Concept Videos
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...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
00:49Ligand Binding and Linkage
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
01:08Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
01:08Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...