丹麦哥本哈根大学David E. Gloriam、Hans Bräuner-Osborne、Alexander S. Hauser以及澳大利亚蒙纳士大学Simon R. Foster等研究人员，合作开发了一个能够将多肽与G蛋白偶联受体（GPCR）配对的分析系统。该研究成果于10月31日发表在《细胞》杂志上。
 
研究人员报道了同源肽和受体的配对。通过在人类A类GPCR的所有蛋白质序列和结构上整合了313种物种的比较基因组学和生物信息学，研究人员确定了揭示额外潜在肽能信号传导系统的通用特征。使用三个正交生化分析，研究人员将17个认为的内源性配体与五个与疾病（包括遗传、肿瘤、神经和生殖系统疾病）相关的孤儿GPCR配对。

研究人员还确定了具有公认的配体和病理生理作用的九种受体的其他多肽。这种综合的计算和多方面的实验方法扩展了多肽与GPCR网络，并为阐明这些信号系统在人类生理学和疾病中的作用开辟了道路。
 
据悉，肽能系统是人类中最丰富的配体—受体介导的信号传导网络。但是，对于大量多肽和超过100种 GPCR，其生理作用仍然难以捉摸。

附：英文原文

Title: Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors

Author: Simon R. Foster, Alexander S. Hauser, Line Vedel, Ryan T. Strachan, Xi-Ping Huang, Ariana C. Gavin, Sushrut D. Shah, Ajay P. Nayak, Linda M. Haugaard-Kedstrm, Raymond B. Penn, Bryan L. Roth, Hans Bruner-Osborne, David E. Gloriam

Issue&Volume: 2019/10/31

Abstract: The peptidergic system is the most abundant network of ligand-receptor-mediated signaling in humans. However, the physiological roles remain elusive for numerous peptides and more than 100 G protein-coupled receptors (GPCRs). Here we report the pairing of cognate peptides and receptors. Integrating comparative genomics across 313 species and bioinformatics on all protein sequences and structures of human class A GPCRs, we identify universal characteristics that uncover additional potential peptidergic signaling systems. Using three orthogonal biochemical assays, we pair 17 proposed endogenous ligands with five orphan GPCRs that are associated with diseases, including genetic, neoplastic, nervous and reproductive system disorders. We also identify additional peptides for nine receptors with recognized ligands and pathophysiological roles. This integrated computational and multifaceted experimental approach expands the peptide-GPCR network and opens the way for studies to elucidate the roles of these signaling systems in human physiology and disease.

DOI: 10.1016/j.cell.2019.10.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31126-2