Structural insights into ligand recognition and selectivity for classes A, B, and C GPCRs.
Structural insights into ligand recognition and selectivity for classes A, B, and C GPCRs.
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DOI：
10.1016/j.ejphar.2015.05.013
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发表时间：
2015-09-15
影响因子：
5
通讯作者：
Pioszak AA
中科院分区：
文献类型：
--
作者：
Lee SM;Booe JM;Pioszak AA
G蛋白偶联受体（GPCR）超家族是细胞表面信号蛋白的最大集合，在人类基因组中有大约800个成员。GPCR几乎调节生理学的所有方面，并且它们是一类重要的药物靶标，市场上约30%的药物靶向GPCR。近年来GPCR结构生物学的突破性进展极大地扩展了我们对GPCR结构和功能的理解，并开创了基于结构的GPCR药物设计的新时代。目前已有近30种不同GPCR的晶体结构，包括A、B、C和F类受体。这些结构为理解GPCR药理学的分子基础提供了基础。在这里，我们审查的配体识别和选择性的GPCR的结构机制，重点是从A类，B和C的选择性的例子，我们强调未来的结构研究的主要悬而未决的问题。
The G protein-coupled receptor (GPCR) superfamily constitutes the largest collection of cell surface signaling proteins with approximately 800 members in the human genome. GPCRs regulate virtually all aspects of physiology and they are an important class of drug targets with ~30% of drugs on the market targeting a GPCR. Breakthroughs in GPCR structural biology in recent years have significantly expanded our understanding of GPCR structure and function and ushered in a new era of structure-based drug design for GPCRs. Crystal structures for nearly thirty distinct GPCRs are now available including receptors from each of the major classes, A, B, C, and F. These structures provide a foundation for understanding the molecular basis of GPCR pharmacology. Here, we review structural mechanisms of ligand recognition and selectivity of GPCRs with a focus on selected examples from classes A, B, and C, and we highlight major unresolved questions for future structural studies.