Allosteric modulation of the G protein-coupled US28 receptor of human cytomegalovirus: are the small-weight inverse agonist of US28 'camouflaged' agonists?

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3744-7. doi: 10.1016/j.bmcl.2014.06.082. Epub 2014 Jul 4.

Abstract

The highly constitutively active G protein-coupled receptor US28 of human cytomegalovirus (HCMV) is thought to camouflage agonism by mediating constitutive endocytosis. With the use of the US28Δ300 mutant, which is largely devoid of constitutive internalization, I have demonstrated that the coupling of the receptor to its downstream signaling partners is responsible for the inverse agonism to agonism efficacy switch in some small-weight ligands of US28.

Keywords: Allosteric modulation; Efficacy switch; G protein-coupled receptor; Human cytomegalovirus; Inverse agonism; US28.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects
  • Chemokine CCL5 / chemistry
  • Chemokine CCL5 / pharmacology*
  • Chemokine CX3CL1 / chemistry
  • Chemokine CX3CL1 / pharmacology*
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Ligands
  • Molecular Structure
  • Molecular Weight
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Receptors, Chemokine / agonists*
  • Receptors, Chemokine / genetics
  • Structure-Activity Relationship
  • Viral Proteins / agonists*
  • Viral Proteins / genetics

Substances

  • Chemokine CCL5
  • Chemokine CX3CL1
  • Ligands
  • Piperidines
  • Receptors, Chemokine
  • US28 receptor, Cytomegalovirus
  • VUF 2274
  • Viral Proteins