Institute of Pharmacy and Biochemistry, Department of Biochemistry, Johann-Joachim-Becherweg 30, 55099 Mainz, Germany.
Eur J Pharmacol. 2012 Feb 15;676(1-3):12-9. doi: 10.1016/j.ejphar.2011.11.041. Epub 2011 Dec 7.
The oxytocin receptor specifically requires cholesterol to maintain and stabilize its high-affinity agonist binding. Here, we applied a receptor chimeric approach to coarsely localize the cholesterol binding domain of the oxytocin receptor. During these studies, we identified the specific dependence on cholesterol as a common property of the oxytocin-vasopressin receptor family. We asked whether the oxytocin receptor maintains or loses its cholesterol dependence when parts of the receptor are exchanged by the corresponding fragments of the cholecystokinin receptor that does not show a specific cholesterol dependence. One of the chimeric receptors revealed full oxytocin binding activity, was capable of signal transduction, and its cholesterol dependence was nearly indistinguishable from that of the oxytocin receptor itself. The data suggest that at least the C-terminal segments of the oxytocin receptor including transmembrane domains 6 and 7 do not participate in cholesterol binding. Thus, the binding sites for the modulator cholesterol and for the agonist oxytocin are therefore most likely colocalized in the N-terminal segment of the oxytocin receptor.
催产素受体特异性地需要胆固醇来维持和稳定其高亲和力激动剂结合。在这里，我们应用受体嵌合方法来粗略定位催产素受体的胆固醇结合域。在这些研究中，我们确定了对胆固醇的特定依赖性是催产素-加压素受体家族的共同特性。我们想知道当催产素受体的部分被不具有特定胆固醇依赖性的胆囊收缩素受体的相应片段交换时，它是否保持或失去其对胆固醇的依赖性。嵌合受体之一显示出完整的催产素结合活性，能够进行信号转导，并且其对胆固醇的依赖性与催产素受体本身几乎无法区分。数据表明，至少包括跨膜域 6 和 7 的催产素受体的 C 末端片段不参与胆固醇结合。因此，调节剂胆固醇和激动剂催产素的结合位点很可能在催产素受体的 N 末端片段中共同定位。
