Domain swapping in the human histamine H1 receptor
| Autor: | Graeme Milligan, Remko A. Bakker, Juan J. Carrillo, Juan F. López-Giménez, Philip G. Strange, Raymond G. Booth, Guido Dees, Rob Leurs |
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| Přispěvatelé: | Medicinal chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Time Factors
Stereochemistry Class C GPCR Histamine H1 receptor Biology Tritium Fluorescence Receptors G-Protein-Coupled Histamine receptor Chlorocebus aethiops Animals Humans Immunoprecipitation Receptors Histamine H1 Binding site Receptor G protein-coupled receptor Pyrilamine Pharmacology Binding Sites Protein Structure Tertiary Transmembrane domain Metabotropic receptor COS Cells Histamine H1 Antagonists Molecular Medicine Energy Metabolism |
| Zdroj: | The Journal of Pharmacology and Experimental Therapeutics, 311(1), 131-8. American Society for Pharmacology and Experimental Therapeutics Bakker, R A, Dees, G, Carrillo, J J, Booth, R G, Lopez-Gimenez, J F, Milligan, G, Strange, P G & Leurs, R 2004, ' Domain swapping in the human histamine H1 receptor ', The Journal of Pharmacology and Experimental Therapeutics, vol. 311, no. 1, pp. 131-8 . https://doi.org/10.1124/jpet.104.067041 |
| ISSN: | 0022-3565 |
| DOI: | 10.1124/jpet.104.067041 |
| Popis: | G-protein-coupled receptors (GPCRs) represent the largest family of receptors involved in transmembrane signaling. Although these receptors were generally believed to be monomeric entities, accumulating evidence supports the presence of GPCRs in multimeric forms. Here, using immunoprecipitation as well as time-resolved fluorescence resonance energy transfer to assess protein-protein interactions in living cells, we unambiguously demonstrate the occurrence of dimerization of the human histamine H(1) receptor. We also show the presence of domain-swapped H(1) receptor dimers in which there is the reciprocal exchange of transmembrane domain TM domains 6 and 7 between the receptors present in the dimer. Mutation of aspartate(107) in transmembrane (TM) 3 or phenylalanine(432) in TM6 to alanine results in two radioligand-binding-deficient mutant H(1) receptors. Coexpression of H(1)D(107) A and H(1)F(432)A, however, results in a reconstituted radioligand binding site that exhibits a pharmacological profile that corresponds to the wild-type H(1) receptor. Interestingly, the H(1) receptor radioligands [(3)H]mepyramine and [(3)H]-(-)-trans-1-phenyl-3-N,N-dimethylamino-1,2,3,4-tetrahydronaphthalene show differential saturation binding values (B(max)) for wild-type H(1) receptors but not for the radioligand binding site that is formed upon coexpression of H(1) D(107)A and H(1) F(432)A receptors, suggesting the presence of different H(1) receptor populations. |
| Databáze: | OpenAIRE |
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