3′,5′-cyclic adenosine monophosphate (cAMP) is well known as a ubiquitous intracellular messenger regulating a diverse array of cellular processes. However, for a group of social amoebae or Dictyostelia undergoing starvation, intracellular cAMP is secreted in a pulsatile manner to their exterior. This then uniquely acts as a first messenger, triggering aggregation of the starving amoebae followed by their developmental progression towards multicellular fruiting bodies formation. Such developmental signalling for extracellularly-acting cAMP is well studied in the popular dictyostelid, Dictyostelium discoideum, and is mediated by a distinct family (‘class E′) of G protein-coupled receptors (GPCRs) collectively designated as the cAMP receptors (cARs). Whilst the biochemical aspects of these receptors are well characterised, little is known about their overall 3D architecture and structural basis for cAMP recognition and subtype-dependent changes in binding affinity. Using a ligand docking-guided homology modelling approach, we hereby present for the first time, plausible models of active forms of the cARs from D. discoideum. Our models highlight some structural features that may underlie the differential affinities of cAR isoforms for cAMP binding and also suggest few residues that may play important roles for the activation mechanism of this GPCR family.

3'，5'-环磷酸腺苷（cAMP）是众所周知的调节各种细胞过程的普遍存在的细胞内信使。但是，对于一群饥饿的社交变形虫或小球藻，细胞内cAMP以搏动的方式分泌到其外部。然后，它独特地充当第一个信使，触发饥饿的变形虫聚集，随后它们向多细胞子实体形成发展。这种在细胞外作用的cAMP的发育信号已经在流行的dictyostelid，Disctyostelium discoideum，并且由G蛋白偶联受体（GPCR）的不同家族（“ E类”）介导，这些家族被统称为cAMP受体（cAR）。尽管这些受体的生化特性已得到很好的表征，但对它们的整体3D结构和cAMP识别以及结合亲和力的亚型依赖性变化的结构基础知之甚少。使用的配体的对接引导同源性建模的方法，我们特此本首次，从汽车的活性形式可信模型D.菌。我们的模型突出了一些结构特征，这些结构特征可能是cAR同工型对cAMP结合的不同亲和力的基础，并且还提出了一些残基，可能对该GPCR家族的激活机制起重要作用。