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Molecular Determinants of Selectivity in 5-Hydroxytryptamine1B Receptor-G Protein Interactions

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Bae, Hyunsu, Anderson, Kristin, Flood, Lori A., Skiba, Nikolai P., Hamm, Heidi E., Graber, Stephen G.·1997·Journal of Biological Chemistry
DOI 10.1074/jbc.272.51.32071
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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-hydroxytryptamine1B (5-HT1B) receptor to discriminate between G protein heterotrimers containing Galphai1 or Galphat. Gi1 can interact with the 5-HT1B receptor and stabilize a high affinity agonist binding state of this receptor, but Gt cannot. A series of Galphat/Galphai1 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 Galphat/Galphai1 chimeras to 5-HT1B receptors using high affinity agonist binding and receptor-stimulated guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding. In the presence of betagamma subunits, amino acid residues 299-318 of Galphai1 increase agonist binding to the 5-HT1B receptor and receptor stimulation of GTPgammaS binding. Moreover, Galphai1 containing only Galphat amino acid sequences from this region does not show any coupling ability to 5-HT1B receptors. Our studies suggest that the alpha4 helix and alpha4-beta6 loop region of Galphas are an important region for specific recognition between receptors and Gi family members.

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Cited by

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Metadata

Authors
Bae, H., Anderson, K., Flood, L. A., Skiba, N. P., Hamm, H. E., & Graber, S. G.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-12
Volume
272
Issue
51
Pages
32071-32077
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.272.51.32071
OpenAlex
W1970405699
Cited by
278
References
0
FWCI
4.84
Type
journal article
Language
en
Open access
hybrid
Licence

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CoChat. (2026). Citation check: Molecular Determinants of Selectivity in 5-Hydroxytryptamine1B Receptor-G Protein Interactions. https://app.cochat.ai/papers/10.1074/jbc.272.51.32071
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Bae, H., Anderson, K., Flood, L. A., Skiba, N. P., Hamm, H. E., & Graber, S. G. (1997). Molecular Determinants of Selectivity in 5-Hydroxytryptamine1B Receptor-G Protein Interactions. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.51.32071

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