期刊
FEBS LETTERS
卷 582, 期 17, 页码 2583-2588出版社
WILEY
DOI: 10.1016/j.febslet.2008.06.030
关键词
G protein-coupled receptor; GPR39; Metal ion; Zn2+ binding site
Ala substitution of potential metal-ion binding residues in the main ligand- binding pocket of the Zn 2+- activated G protein- coupled receptor 39 ( GPR39)receptor did not decrease Zn 2+ potency. In contrast, Zn 2+ stimulation was eliminated by combined substitution of His 17 and His 19, located in the N- terminal segment. Surprisingly, substitution of Asp 313 located in extracellular loop 3 greatly increased ligand- independent signaling and apparently eliminated Zn 2+- induced activation. It is proposed that Zn 2+ acts as an agonist for GPR39, not in the classical manner by directly stabilizing an active conformation of the transmembrane domain, but instead by binding to His 17 and His 19 in the extracellular domain and potentially by diverting Asp 313 from functioning as a tethered inverse agonist through engaging this residue in a tridentate metal- ion binding site. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据