Characterization of the hormone binding site of natriuretic peptide receptor‐C

FEBS Letters

Engel, Alfred M¹  Lowe, David G¹ 

[1] Cardiovascular Research Dept. Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080, USA

关键词: Atrial natriuretic peptide;    Natriuretic peptide receptor;    Mutagenesis;    Receptor/hormone interaction;    ANP;    atrial natriuretic peptide;    BNP;    brain natriuretic peptide;    CNP;    C-type natriuretic peptide;    rANP;    rat ANP (28 amino acids);    hANP;    human ANP (28 amino acids);    rBNP;    rat BNP (32 amino acids);    hBNP;    human BNP (32 amino acids);    cANF;    des[Gln18;    Ser19;    Gly20;    Leu21 Gly22]ANF4-23-NH2;    NPR;    natriuretic peptide receptor;    IgG;    Immunoglobulin G;    C-IgG;    NPR-C extracellular domain/IgG Fc fusion protein;   

DOI  :  10.1016/0014-5793(95)00096-R

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The hormone binding site of rat and human natriuretic peptide clearance receptor (NPR-C), a single transmembrane receptor, has been further refined by mutagenesis. In addition to residue 188 (rat Ala, human Ile), which completely inverts the pharmacology of the rat and human receptors [Engel et al. (1994) J. Biol. Chem. 269, 17005–17008], we report a second key residue at position 205 (rat Tyr, human Asn) which modulates affinity to a limited number of ligands. Orthologous mutation of both residues results in tighter binding for human and weaker binding for rat NPR-C. The ligand binding fold of the receptor is formed by at least the first half of the extracellular domain containing two intramolecular disulfide loops, with the two affinity-modulating residues 188 and 205 in the second loop.

【 授权许可】

Unknown