ISSN:
0887-3585
Keywords:
β-adrenergic recepor
;
chimeric proteins
;
receptor subtypes
;
ligand binding
;
protein structure-function
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
Pharmacological analysis of ligand binding to the β-adrenergic receptor (βAR) has revealed the existence of two distinct receptor subtypes (β1 and β2) which are the products of different genes. The predicted amino acid sequence of the β1 and β2 receptors differ by 48%. To identify the regions of the proteins responsible for determining receptor subtype, chimeras were constructed from domains of the human β1 and hamster β2 receptors. Analyses of the ligand-binding characteristics of these hybrid receptors revealed that residues in the middle portion of the βAR sequence, particularly around transmembrane regions 4 and 5, contribute to the subtype specific binding of agonists. Smaller molecular replacement of regions of the hamster β2AR with the analogous regions from the avian β1AR, however, failed to identify any single residue substitution capable of altering the subtype specificity of the receptor. These data indicate that, whereas sequences around transmembrane regions 4 and 5 may contribute to conformations which influence the ligand-binding properties of the receptor, the subtype-specific differences in amine-substituted agonist binding cannot be attributed to a single molecular interaction between the ligand and any amino acid residue which is divergent between the β1 and β2 receptors.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/prot.340060309
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