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Linking agonist binding to histamine H1 receptor activation.
- Source :
-
Nature chemical biology [Nat Chem Biol] 2005 Jul; Vol. 1 (2), pp. 98-103. Date of Electronic Publication: 2005 Jun 19. - Publication Year :
- 2005
-
Abstract
- G protein-coupled receptors (GPCRs) constitute a large and functionally diverse family of transmembrane proteins. They are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways and are among the most targeted proteins in drug discovery. The detailed molecular mechanism for agonist-induced activation of rhodopsin-like GPCRs has not yet been described. Using a combination of site-directed mutagenesis and molecular modeling, we characterized important steps in the activation of the human histamine H1 receptor. Both Ser3.36 and Asn7.45 are important links between histamine binding and previously proposed conformational changes in helices 6 and 7. Ser3.36 acts as a rotamer toggle switch that, upon agonist binding, initiates the activation of the receptor through Asn7.45. The proposed transduction involves specific residues that are conserved among rhodopsin-like GPCRs.
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
Histamine Agonists chemistry
Humans
Models, Molecular
Mutation genetics
Protein Structure, Tertiary
Receptors, Histamine H1 genetics
Serine genetics
Serine metabolism
Histamine Agonists metabolism
Histamine Agonists pharmacology
Receptors, Histamine H1 chemistry
Receptors, Histamine H1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4450
- Volume :
- 1
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 16408006
- Full Text :
- https://doi.org/10.1038/nchembio714