Gly166 in the NK1 receptor regulates tachykinin selectivity and receptor conformation.
FEBS Lett
; 416(3): 335-8, 1997 Oct 27.
Article
em En
| MEDLINE
| ID: mdl-9373180
ABSTRACT
We have studied the pharmacological properties of genetically engineered human NK1 tachykinin receptors in which residues at the extracellular surface of the fourth transmembranal domain were substituted with the corresponding amino acids from the NK2 receptor. We show that substitution of G166CY167F in the human NK1 receptor induces high affinity binding of a group of tachykinin ligands, known as 'septides' (i.e. neurokinin A, neurokinin B, [pGlu6,Pro9]-substance P6-11 and substance P-methylester). In contrast, binding of substance P and non-peptide antagonists is unaffected by these mutations. This effect parallels that found on the rat receptor and is therefore species specific. Second, we demonstrate that mutation of Gly166 to Cys alone is both necessary and sufficient to create this pan-reactive tachykinin receptor, whereas replacement of Tyr167 by Phe has no detectable effect on the pharmacological properties of the receptor. Furthermore, analysis of the effect of N-ethylmaleimide and dithiothreitol on binding of radiolabelled substance P documents differences in the mode in which this ligand interacts with wild-type and mutant receptors and supports the existence of a mutational induced change in the conformational status of the NK1 receptor.
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Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
/
Receptores da Neurocinina-1
/
Glicina
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article