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Date: 19 December 1997

Journal: Journal of Biological Chemistry Volume 272, Issue 51, 19 December 1997, Pages 32071-32077 , Doi: 10.1074/jbc.272.51.32071

1997 | Molecular determinants of selectivity in 5-hydroxytryptamine(1B) receptor-G protein interactions…

Bae, H.ab, Anderson, K.c, Flood, L.A.c, Skiba, N.P.a, Hamm, H.E.a, Graber, S.G.cd

첨부파일

Abstract

The recognition between G protein and cognate receptor plays a key role in specific cellular responses to environmental stimuli. Here we explore specificity in receptor-G protein coupling by taking advantage of the ability of the 5-hydroxytryptamine(1B) (5-HT(1B)) receptor to discriminate between G protein heterotrimers containing Gα(i1) or Gα(t). G(i1) can interact with the 5-HT(1B) receptor and stabilize a high affinity agonist binding state of this receptor, but G(t) cannot. A series of Gα(t)/Gα(i1) chimeric proteins have been generated in Escherichia coli, and their functional integrity has been reported previously (Skiba, N. P., Bae, H., and Hamm, H. E. (1996) J. Biol. Chem. 271, 413-424). We have tested the functional coupling abilities of the Gα(t)/Gα(i1) chimeras to 5-HT(1B) receptors using high affinity agonist binding and receptor-stimulated guanosine 5'-3-O-(thio)triphosphate (GTPγS) binding. In the presence of βγ subunits, amino acid residues 299- 318 of Gα(i1) increase agonist binding to the 5-HT(1B) receptor and receptor stimulation of GTPγS binding. Moreover, Ga(i1) containing only Gα(t) amino acid sequences from this region does not show any coupling ability to 5- HT(1B) receptors. Our studies suggest that the α4 helix and α4-β6 loop region of Gαs are an important region for specific recognition between receptors and G(i) family members.


Indexed keywords

EMTREE drug terms: guanine nucleotide binding protein; serotonin 1b receptor

EMTREE medical terms: article; molecular dynamics; molecular interaction; molecular recognition; nonhuman; priority journal; protein conformation; protein protein interaction; receptor affinity

MeSH: Amino Acid Sequence; Binding Sites; Catalysis; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Diphosphate; Guanosine Triphosphate; Molecular Sequence Data; Protein Binding; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin; Recombinant Fusion Proteins; Sequence Homology, Amino Acid
Medline is the source for the MeSH terms of this document.


Chemicals and CAS Registry Numbers: GTP-Binding Proteins, EC 3.6.1.-; Guanosine 5'-O-(3-Thiotriphosphate), 37589-80-3; Guanosine Diphosphate, 146-91-8; Guanosine Triphosphate, 86-01-1; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin; Recombinant Fusion Proteins


ISSN: 00219258 CODEN: JBCHASource Type: Journal Original language: English
Doi: 10.1074/jbc.272.51.32071 PubMed ID: 9405403 Document Type: Article
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