16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Structural features for functional selectivity at serotonin receptors.

      Science (New York, N.Y.)

      Amino Acid Motifs, Amino Acid Sequence, Arrestin, metabolism, Arrestins, Binding Sites, Crystallography, X-Ray, Ergolines, chemistry, Ergotamine, HEK293 Cells, Humans, Ligands, Lysergic Acid Diethylamide, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Secondary, Receptor, Serotonin, 5-HT1B, Receptor, Serotonin, 5-HT2B, Receptors, Serotonin, Signal Transduction

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or noncanonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies showing that the hallucinogen lysergic acid diethylamide, its precursor ergotamine (ERG), and related ergolines display strong functional selectivity for β-arrestin signaling at the 5-HT2B 5-hydroxytryptamine (5-HT) receptor, whereas they are relatively unbiased at the 5-HT1B receptor. To investigate the structural basis for biased signaling, we determined the crystal structure of the human 5-HT2B receptor bound to ERG and compared it with the 5-HT1B/ERG structure. Given the relatively poor understanding of GPCR structure and function to date, insight into different GPCR signaling pathways is important to better understand both adverse and favorable therapeutic activities.

          Related collections

          Author and article information

          Journal
          23519215
          3644390
          10.1126/science.1232808

          Comments

          Comment on this article