Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor
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Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor. / Rosenkilde, M M; Lucibello, M; Holst, B; Schwartz, T W.
I: FEBS Letters, Bind 439, Nr. 1-2, 1998, s. 35-40.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor
AU - Rosenkilde, M M
AU - Lucibello, M
AU - Holst, B
AU - Schwartz, T W
N1 - Keywords: Amino Acid Sequence; Animals; Binding, Competitive; COS Cells; Histidine; Humans; Membrane Proteins; Molecular Sequence Data; Mutation; Neurokinin B; Protein Conformation; Receptors, Tachykinin; Zinc
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 9849872
VL - 439
SP - 35
EP - 40
JO - F E B S Letters
JF - F E B S Letters
SN - 0014-5793
IS - 1-2
ER -
ID: 10536610