Laboratory of Animal Biochemistry, Faculty of Applied Biological Sciences, Gifu University, Gifu Shi, Gifu, Japan.
Hypertens Res. 2010 Feb;33(2):91-7. doi: 10.1038/hr.2009.201. Epub 2009 Nov 27.
The discovery of (pro)renin receptor, (P)RR, has made the renin-angiotensin system (RAS) more multifaceted. Interaction of renin and prorenin with this receptor has set a new perspective about the physiological functions, activation mechanism and pathophysiological roles of renin/prorenin. Uses of peptides mimicking the structure of the ligands have been very effective for determining structure-function relationship between the ligands and receptor. The probable pivotal role of decoy peptide region (R(10P)IFLKRMPSI(19P)) of prorenin prosegment was suggested for higher binding affinity of prorenin to (P)RR than that of mature renin. Recently, 'hinge' region peptide (S(149)QGVLKEDVF(158)) in renin/prorenin molecule has been reported. Bothrenin and prorenin can interact with (P)RR through the 'hinge' region. Furthermore, it has been proposed that prorenin has multiple binding sites whereas renin has a single binding site for (P)RR. To comprehend the activation mechanism of renin and prorenin after receptor binding, it is very important to understand their interaction with the receptor. Several kinds of peptides designed from the regions of the tertiary structure of renin and predicted model of prorenin facilitated the study of the in vitro binding mechanisms for renin and prorenin to (P)RR. Here, a series of recent in vitro studies was reviewed to discuss a possible binding mechanism of renin/prorenin to the (P)RR.
(前)肾素受体((P)RR)的发现使肾素-血管紧张素系统(RAS)更加多面化。肾素和前肾素与该受体的相互作用为肾素/前肾素的生理功能、激活机制和病理生理作用设定了新的视角。模拟配体结构的肽的使用对于确定配体与受体之间的结构-功能关系非常有效。前肾素前肽(R(10P)IFLKRMPSI(19P))的诱饵肽区域可能起着关键作用,使前肾素与 (P)RR 的结合亲和力高于成熟肾素。最近,报道了肾素/前肾素分子中的“铰链”区肽(S(149)QGVLKEDVF(158))。肾素和前肾素都可以通过“铰链”区与 (P)RR 相互作用。此外,有人提出前肾素具有多个结合位点,而肾素只有一个结合位点用于与 (P)RR 结合。为了理解受体结合后肾素和前肾素的激活机制,了解它们与受体的相互作用非常重要。从肾素的三级结构区域和前肾素的预测模型设计的几种肽促进了对肾素和前肾素与 (P)RR 体外结合机制的研究。在这里,回顾了一系列最近的体外研究,以讨论肾素/前肾素与 (P)RR 结合的可能机制。