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| A peptide derived from a beta(2)-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation |
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| Author(s): Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, Bouvier M |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 271 Issue: 27 Pages: 16384-16392 Published: JUL 5 1996 |
| Times Cited: 440 References: 78 |
| Abstract: One of the assumptions of the mobile receptor hypothesis as it relates to G protein-coupled receptors is that the stoichiometry of receptor, G protein, and effector is 1:1:1 (Bourne, H. R,, Sanders, D, A, and McCormick, F, (1990) Nature 348, 125-132), Many studies on the cooperativity of agonist binding are incompatible with this notion and have suggested that both G proteins and their associated receptors can be oligomeric. However, a clear physical demonstration that G protein-coupled receptors can indeed interact as dimers and that such interactions may have functional consequences was lacking, Here, using differential epitope tagging we demonstrate that beta(2)-adrenergic receptors do form SDS-resistant homodimers and that transmembrane domain VI of the receptor may represent part of an interface for receptor dimerization, The functional importance of dimerization is supported by the observation that a peptide derived from this domain that inhibits dimerization also inhibits beta-adrenergic agonist-promoted stimulation of adenylyl cyclase activity. Moreover, agonist stimulation was found to stabilize the dimeric state of the receptor, while inverse agonists favored the monomeric species, which suggests that interconversion between monomeric and dimeric forms may be important for biological activity. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MONTREAL, DEPT BIOCHIM, MONTREAL, PQ H3C 3J7 CANADA
2. UNIV MONTREAL, GRP RECH SYST NERVEUX AUTONOME, MONTREAL, PQ H3C 3J7 CANADA
3. HOP SACRE COEUR, CTR RECH, MONTREAL, PQ H4J 1C5 CANADA
4. UNIV MONTREAL, DEPT MED, MONTREAL, PQ H4J 1C5 CANADA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: UW352 |
| ISSN: 0021-9258 |
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