Structure-function studies of the eighth hydrophobic domain of a serotonin receptor

Joyce H. Hurley, Laura J. Bloem, Fred Pavalko, Jian Liu, Mingting Tian, Jay R. Simon, Lei Yu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The most prominent structural feature of the G protein-coupled receptor superfamily is their seven hydrophobic domains, which are postulated to form membrane-spanning α helices. Some members of the G protein-coupled receptor family, specifically several serotonin (5-HT) receptors, possess eight hydrophobic domains. The importance of this extra hydrophobic domain, located at the N terminus of the receptor, is unknown. This question was addressed by deleting the extrahydrophobic region from the 5-HT(2C) receptor and comparing its function and topology with those of the wild-type receptor. Immunofluorescence microscopy was used to determine the location of the N terminus of the epitope-tagged wild-type and mutant receptors. The N terminus of both receptors was extracellular, suggesting that the extra hydrophobic domain does not change the topology of this receptor and is unlikely to be a membrane-spanning α helix. Radioligand-binding studies in transfected cells and expression studies in Xenopus oocytes demonstrated that seven hydrophobic domains were sufficient for normal function in these assays. Interestingly, the mutant receptor, now containing seven hydrophobic domains, is expressed at higher levels in transfected cells than the wild-type receptor containing eight hydrophobic domains, suggesting that the extra hydrophobic domain does impact the activity of this receptor by regulating its expression.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalJournal of neurochemistry
Issue number1
StatePublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience


  • G protein-coupled receptor
  • Hydrophobic domain
  • Topology
  • α helix


Dive into the research topics of 'Structure-function studies of the eighth hydrophobic domain of a serotonin receptor'. Together they form a unique fingerprint.

Cite this