4.7:
Ligand Binding and Linkage
Most proteins have multiple locations where ligands can associate, in addition to the site responsible for protein function. Binding of a molecule to any of these sites often results in conformational changes, altering the shape of the protein.
When this change affects the binding of another ligand, the two sites are described as coupled or linked. The binding site linkage can be positively or negatively regulated.
In a positive linkage, the binding of one ligand results in conformational changes that make another site more likely to bind to its respective ligand.
In a negative linkage, the binding of one ligand results in conformational changes that prevent another binding site from associating with its ligand.
4.7:
Ligand 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 active site of the protein.
Binding site linkages can cause either positive or negative regulation of ligand binding to other sites. In cases where both ligands prefer to bind to the same conformation of a protein, binding at one site increases the affinity of the other site for its respective ligand. This is known as a positive linkage. On the other hand, if the ligands prefer binding to different conformations, binding of one ligand will make it difficult for the second ligand to bind to the protein. This is known as a negative linkage.
Suggested Reading
- Suplatov, D., & Švedas, V. (2015). Study of Functional and Allosteric Sites in Protein Superfamilies. Acta naturae, 7(4), 34–45.
- Bellelli, A. and Carey, J. (2017). Proteins with Multiple Bindin Sites. In Reversible Ligand Binding (eds A. Bellelli and J. Carey). doi:10.1002/9781119238508.ch4
- Helmstaedt, K., Krappmann, S., & Braus, G. H. (2001). Allosteric regulation of catalytic activity: Escherichia coli aspartate transcarbamoylase versus yeast chorismate mutase. Microbiology and molecular biology reviews : MMBR, 65(3), 404–421. doi:10.1128/MMBR.65.3.404-421.2001