阿片受體家族包含3個（μ-,、δ-和κ-阿片受體）成員,，他們屬于G蛋白偶聯(lián)受體超家族（GPCR）。 除止痛作用外,，δ-阿片受體（δ-OR）在神經(jīng)學(xué)上的其它功能仍不是很清楚,。
5月16日，國際著名期刊Nature在線發(fā)表了斯坦福大學(xué)醫(yī)學(xué)院等科研單位的題為Structure of the δ-opioid receptor bound to naltrindole的研究論文,，報道了鼠δ-OR與亞型選擇性拮抗劑納曲吲哚結(jié)合的晶體結(jié)構(gòu),。
結(jié)構(gòu)顯示，阿片配基的結(jié)合口袋可分為兩個明顯不同的部位：結(jié)合口袋的下方在阿片受體中高度保守,；上方的氨基酸殘基相異,，決定亞型選擇性。這為阿片受體藥劑學(xué)的“message–address”模型提供了結(jié)構(gòu)上的解釋和證實(shí),，在這個模型中,，不同的“message”（效力）和“address”（選擇性）包含在配基中。
通過比較δ-OR與其它GPCRs的“address”區(qū)域顯示這個結(jié)構(gòu)組成可能是一個更普遍的現(xiàn)象,。(生物谷Bioon.com）
doi：10.1038/nature11111
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PMID:
Structure of the δ-opioid receptor bound to naltrindole
Sébastien Granier,，Aashish Manglik，Andrew C. Kruse,，Tong Sun Kobilka,，F(xiàn)oon Sun Thian，William I. Weis& Brian K. Kobilka
Department of Molecular and Cellular Physiology,， Stanford University School of Medicine,，Stanford，California 94305,， USA
CNRS UMR 5203,， and INSERM U661， and Université Montpellier 1 et 2,， Institut de Génomique Fonctionnelle,， Montpellier 34094， France
Department of Structural Biology,， Stanford University School of Medicine,， Stanford， California
The opioid receptor family comprises three members,， the μ-,， δ- and κ-opioid receptors,， which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily， and are excellent therapeutic targets for pain control. The δ-opioid receptor (δ-OR) has a role in analgesia,， as well as in other neurological functions that remain poorly understood1. The structures of the μ-OR and κ-OR have recently been solved2,， 3. Here we report the crystal structure of the mouse δ-OR， bound to the subtype-selective antagonist naltrindole. Together with the structures of the μ-OR and κ-OR,， the δ-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors,， the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the ‘message–address’ model of opioid receptor pharmacology，in which distinct‘message’ (efficacy) and ‘address’ (selectivity) determinants are contained within a single ligand. Comparison of the address region of the δ-OR with other GPCRs reveals that this structural organization may be a more general phenomenon,，extending to other GPCR families as well.
