Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | FEBS Letters |
Volume | 439 |
Issue number | 1-2 |
Pages (from-to) | 35-40 |
Number of pages | 5 |
ISSN | 0014-5793 |
Publication status | Published - 1998 |
Bibliographical note
Keywords: Amino Acid Sequence; Animals; Binding, Competitive; COS Cells; Histidine; Humans; Membrane Proteins; Molecular Sequence Data; Mutation; Neurokinin B; Protein Conformation; Receptors, Tachykinin; Zinc
ID: 10536610