Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor

FEBS Lett. 1998 Nov 13;439(1-2):35-40. doi: 10.1016/s0014-5793(98)01331-3.


In the wild-type tachykinin NK3A receptor histidyl residues are present at two positions in TM-V, V:01 and V:05, at which Zn2+ functions as an antagonist in NK1 and kappa-opioid receptors with engineered metal-ion sites. Surprisingly, in the NK3A receptor Zn2+ instead increased the binding of the agonist 125I-[MePhe7]neurokinin B to 150%. [MePhe7]neurokinin B bound to the NK3A receptor in a two-component mode of which Zn2+ eliminated the subnanomolar binding mode but induced a higher binding capacity of the nanomolar binding mode. Signal transduction was not induced by ZnCl2 but 10 microM ZnCl2 enhanced the effect of neurokinin B. Ala-substitution of HisV:01 eliminated the enhancing effect of Zn2+ on peptide binding. It is concluded that physiological concentrations of Zn2+ have a positive modulatory effect on the binding and function of neurokinin B on the NK3A receptor through a bis-His site in TM-V.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding, Competitive
  • COS Cells
  • Histidine / chemistry*
  • Humans
  • Membrane Proteins / chemistry*
  • Molecular Sequence Data
  • Mutation
  • Neurokinin B / pharmacology*
  • Protein Conformation
  • Receptors, Tachykinin / agonists*
  • Receptors, Tachykinin / chemistry*
  • Receptors, Tachykinin / genetics
  • Zinc / chemistry*


  • Membrane Proteins
  • Receptors, Tachykinin
  • Histidine
  • Neurokinin B
  • Zinc