Sommer Martha E, Selent Jana, Carlsson Jens, De Graaf Chris, Gloriam David E, Keseru Gyorgy M, Kosloff Mickey, Mordalski Stefan, Rizk Aurelien, Rosenkilde Mette M, Sotelo Eddy, Tiemann Johanna K S, Tobin Andrew, Vardjan Nina, Waldhoer Maria, Kolb Peter
Institute of Medical Physics and Biophysics, Charité-Universitätsmedizin Berlin, Berlin, 10117, Germany.
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, 13125, Germany.
ACS Pharmacol Transl Sci. 2020 Mar 31;3(2):361-370. doi: 10.1021/acsptsci.0c00024. eCollection 2020 Apr 10.
G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function. The success of GLISTEN, coupled with new findings and paradigm shifts in the field, led in 2019 to the creation of a related consortium called ERNEST (COST Action CA18133). ERNEST broadens focus to entire signaling cascades, based on emerging ideas of how complexity and specificity in signal transduction are not determined by receptor-ligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting.
G蛋白偶联受体（GPCRs）因其作为药物靶点的治疗潜力而受到深入研究。这个跨膜受体蛋白大家族的成员介导多种细胞类型中的信号转导，并在人类生理和健康中发挥关键作用。2013年，研究联盟GLISTEN（成本行动CM1207）成立，其目标是利用GPCR结构和动力学知识的大幅增长，推动GPCR功能分子调节剂的开发。GLISTEN的成功，再加上该领域的新发现和范式转变，在2019年促成了一个名为ERNEST（成本行动CA18133）的相关联盟的成立。基于信号转导中的复杂性和特异性并非仅由受体-配体相互作用决定的新观点，ERNEST将重点扩大到整个信号级联反应。一种将研究界的各种数据和观点整合到一个单一多维图谱中的整体方法，对于改进药物设计和治疗靶点具有巨大的前景。
