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

FEBS Letters

Holst, Birgitte¹  Schwartz, Thue W¹  Rosenkilde, Mette M¹  Lucibello, Maria¹ 

[1] Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute 18.6, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark

关键词: Metal ion;    Tachykinin receptor;    Zinc;    7TM receptor;   

DOI  :  10.1016/S0014-5793(98)01331-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In the wild-type tachykinin NK_3A 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 κ-opioid receptors with engineered metal-ion sites. Surprisingly, in the NK_3A receptor Zn²⁺ instead increased the binding of the agonist ¹²⁵I-[MePhe⁷]neurokinin B to 150%. [MePhe⁷]neurokinin B bound to the NK_3A 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 μM 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 NK_3A receptor through a bis-His site in TM-V.

【 授权许可】

Unknown