On the role of extracellular loops of opioid receptors in conferring ligand selectivity

Thomas G. Metzger, David M. Ferguson

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Based on an analysis of results taken from site-directed mutagenesis studies performed on opioid receptors, a role for the extracellular loops in conferring opioid subtype selectivity is proposed. It is suggested that the extracellular loop regions (which represent the region of highest sequence variability among opioid subtypes) interact with opioid ligands in a primarily non-specific fashion. Although these interactions are non-specific, they appear to play a discriminatory role in ligand binding and, in certain cases, prevent particular ligands from binding among receptor subtypes. We propose that selectivity may be imparted through a mechanism of exclusion, rather than specific pharmacophore recognition within the extracellular loops and N-terminal domain. This hypothesis is supported by a careful analysis of the binding profiles of several selective and non-selective ligands to a variety of chimeric mutants. These results, when combined with results taken from single-point mutation experiments point to the existence of a high affinity binding pocket within the transmembrane region which may be common among the opioid subtypes.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalFEBS Letters
Volume375
Issue number1-2
DOIs
StatePublished - Nov 13 1995

Keywords

  • Chimeric receptor
  • DAMGO
  • Extracellular loops
  • Ligand binding
  • Opioid receptor

Fingerprint Dive into the research topics of 'On the role of extracellular loops of opioid receptors in conferring ligand selectivity'. Together they form a unique fingerprint.

Cite this