PRESTO-Tango作为一种用于研究可成药人类G蛋白偶联受体组的开源资源。
PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome.
作者信息
Kroeze Wesley K, Sassano Maria F, Huang Xi-Ping, Lansu Katherine, McCorvy John D, Giguère Patrick M, Sciaky Noah, Roth Bryan L
机构信息
1] Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA. [2] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Pharmacology, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, USA.
出版信息
Nat Struct Mol Biol. 2015 May;22(5):362-9. doi: 10.1038/nsmb.3014. Epub 2015 Apr 20.
G protein-coupled receptors (GPCRs) are essential mediators of cellular signaling and are important targets of drug action. Of the approximately 350 nonolfactory human GPCRs, more than 100 are still considered to be 'orphans' because their endogenous ligands remain unknown. Here, we describe a unique open-source resource that allows interrogation of the druggable human GPCRome via a G protein-independent β-arrestin-recruitment assay. We validate this unique platform at more than 120 nonorphan human GPCR targets, demonstrate its utility for discovering new ligands for orphan human GPCRs and describe a method (parallel receptorome expression and screening via transcriptional output, with transcriptional activation following arrestin translocation (PRESTO-Tango)) for the simultaneous and parallel interrogation of the entire human nonolfactory GPCRome.
G蛋白偶联受体（GPCRs）是细胞信号传导的重要介质，也是药物作用的重要靶点。在大约350种非嗅觉人类GPCR中，超过100种仍被认为是“孤儿受体”，因为它们的内源性配体尚不清楚。在这里，我们描述了一种独特的开源资源，它允许通过一种不依赖G蛋白的β-抑制蛋白招募试验来研究可成药的人类GPCR组。我们在120多个非孤儿人类GPCR靶点上验证了这个独特的平台，证明了它在发现孤儿人类GPCR新配体方面的效用，并描述了一种方法（通过转录输出进行平行受体组表达和筛选，在抑制蛋白易位后进行转录激活（PRESTO-Tango）），用于同时并行研究整个人类非嗅觉GPCR组。
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