Identification of residues required for ligand binding to the. beta. -adrenergic receptor

Journal Article · Wed Jul 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.13.4384· OSTI ID:5316642

Strader, C D; Sigal, I S; Register, R B; Candelore, M R; Rands, E; Dixon, R A.F.

The functional significance of conserved polar amino acids within the putative transmembrane region of the ..beta..-adrenergic receptor (..beta..AR) was examined by oligonucleotide-directed mutagenesis of the hamster gene encoding ..beta..AR and expression of the mutant genes in COS-7 cells. Although a substitution of aspartate at position 113 with an asparagine residue did not affect expression or processing of the protein, the resulting mutant ..beta..AR did not show detectable binding toward the antagonist (/sup 125/I)-iodocyanopindolol. Replacement of the aspartate and asparagine residues at positions 79 and 318, respectively, had no effect on the affinity of the receptor toward antagonists but reduced the affinity of the receptor toward agonist by 1 order of magnitude. Furthermore, the authors observed that substitution of the proline at position 323 with a serine residue resulted in improper or incomplete processing of the ..beta..AR, presumably reflecting a role for this residue in the folding of the receptor. Together with previous results from deletion mutagenesis studies, these observations indicate that the ligand binding site involves the transmembrane region of the ..beta..AR.

• Research Organization: Merck Sharp and Dohme Research Labs., West Point, PA (USA)
• OSTI ID: 5316642
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:13; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMIDES
AMINES
AMINO ACIDS
ANIMALS
AROMATICS
ASPARAGINE
ASPARTIC ACID
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
CARBOXYLIC ACIDS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
GENES
HAMSTERS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MUTAGENESIS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROLINE
PROTEINS
PYRROLES
PYRROLIDINES
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RODENTS
SERINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES