Receptor mutagenesis

Conserved residues in the intracellular parts of a receptor are more likely to be involved in G-protein binding and signal transduction. This is the case for the DRY motif, a highly conserved amino acid sequence that, with the exception of some conservative mutations, is present in all rhodopsin-like receptors [1], 

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Table 7. Receptor Mutagenesis Data (WT = Wild-Type Activity)...

Westkaemper RB, Glennon RA. Application of ligand SAR, receptor modeling and receptor mutagenesis to the discovery and development of a new class of 5-HT(2A) ligands. Curr Topics Med Chem 2002 2 575-598. 

Ganguli SC, Park CG, Holtmann MH, Hadac EM, Kenakin TP, Miller LJ. Protean effects of a natural peptide agonist of the G protein-coupled secretin receptor demonstrated by receptor mutagenesis. J Pharmacol Exp Ther 1998 286 593-598. 

Kolakowski, L. F., Jr., Lu, B., Gerard, C., and Gerard, N. P. (1995). Probing the message address sites for chemoattractant binding to the G5a receptor. Mutagenesis of hydrophilic and proline residues within the transmembrane segments / Biol. Chem. 270, 18077-18082. 

The combination of receptor mutagenesis and ligand modification helps to elucidate specific interactions between residues of the ligand and residues within the receptor sequence. 

Keywords Cannabinoid receptor - Mutagenesis - Polymorphism - Gene regulation, binding... 

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