Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors.
Structure and mechanism for recognition of peptide hormones by Class B G-protein-coupled receptors.
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DOI：
10.1038/aps.2011.170
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发表时间：
2012-03
影响因子：
8.2
通讯作者：
Xu, H. Eric
中科院分区：
文献类型：
--
作者：
Pal, Kuntal;Melcher, Karsten;Xu, H. Eric
B类g蛋白偶联受体（gpcr）是肽激素的受体，包括胰高血糖素、甲状旁腺激素和降钙素。这些受体参与广泛的生理活动，从代谢调节和应激控制到骨骼系统的发育和维持。因此，它们是治疗糖尿病、骨质疏松症和压力相关疾病的重要药物靶点。B类gpcr被组织成两个模块结构域：细胞外结构域（ECD）和包含7个跨膜螺旋的螺旋束（TM结构域）。ECD负责激素结合的高亲和力和特异性，而TM结构域是受体激活和下游g蛋白信号偶联所必需的。尽管全长受体的结构尚不清楚，但许多B类gpcr的ECD结构已被很好地表征，揭示了配体识别的共同折叠。本文综述了指导B类ECDs结合激素的一般结构原理及其在设计用于治疗目的的肽激素类似物中的意义。
Class B G-protein-coupled receptors (GPCRs) are receptors for peptide hormones that include glucagon, parathyroid hormone, and calcitonin. These receptors are involved in a wide spectrum of physiological activities, from metabolic regulation and stress control to development and maintenance of the skeletal system. As such, they are important drug targets for the treatment of diabetes, osteoporosis, and stress related disorders. Class B GPCRs are organized into two modular domains: an extracellular domain (ECD) and a helical bundle that contains seven transmembrane helices (TM domain). The ECD is responsible for the high affinity and specificity of hormone binding, and the TM domain is required for receptor activation and signal coupling to downstream G-proteins. Although the structure of the full-length receptor remains unknown, the ECD structures have been well characterized for a number of Class B GPCRs, revealing a common fold for ligand recognition. This review summarizes the general structural principles that guide hormone binding by Class B ECDs and their implications in the design of peptide hormone analogs for therapeutic purposes.
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