Abstract：
The bioinformatic analysis of cannabinoid receptors (CBRs) CB1 and CB2 reveals a detailed picture of their structure, evolution, and physiological significance within the endocannabinoid system (ECS). The study highlights the evolutionary conservation of these receptors evidenced by sequence alignments across diverse species including humans, amphibians, and fish. Both CBRs share a structural hallmark of seven transmembrane (TM) helices, characteristic of class A G-protein-coupled receptors (GPCRs), which are critical for their signalling functions. The study reports a similarity of 44.58 % between both CBR sequences, which suggests that while their evolutionary paths and physiological roles may differ, there is considerable conservation in their structures. Pathway databases like KEGG, Reactome, and WikiPathways were employed to determine the involvement of the receptors in various signalling pathways. The pathway analyses integrated within this study offer a detailed view of the CBRs interactions within a complex network of cannabinoid-related signalling pathways. High-resolution crystal structures (PDB ID: 5U09 for CB1 and 5ZTY for CB2) provided accurate structural information, showing the binding pocket volume and surface area of the receptors, essential for ligand interaction. The comparison between these receptors\' natural sequences and their engineered pseudo-CBRs (p-CBRs) showed a high degree of sequence identity, confirming the validity of using p-CBRs in receptor-ligand interaction studies. This comprehensive analysis enhances the understanding of the structural and functional dynamics of cannabinoid receptors, highlighting their physiological roles and their potential as therapeutic targets within the ECS.
摘要：
大麻素受体（CBRs）CB1和CB2的生物信息学分析揭示了它们的详细结构，进化,和内源性大麻素系统（ECS）内的生理意义。该研究强调了这些受体的进化保守性，这通过包括人类在内的不同物种的序列比对得到了证明。两栖动物,和鱼。两种CBR都具有七个跨膜（TM）螺旋的结构标志，A类G蛋白偶联受体（GPCRs）的特征，这对它们的信号功能至关重要。该研究报告两个CBR序列之间的相似性为44.58％，这表明尽管它们的进化路径和生理角色可能不同，他们的结构有相当大的保护作用。像KEGG这样的路径数据库，Reactome,和WikiPathways被用来确定受体在各种信号通路中的参与。本研究中整合的途径分析提供了大麻素相关信号通路复杂网络中CBRs相互作用的详细视图。高分辨率晶体结构（PDBID：CB1为5U09，CB2为5ZTY）提供了准确的结构信息，显示受体的结合袋体积和表面积，对于配体相互作用至关重要。这些受体的天然序列和它们的工程伪CBRs（p-CBRs）之间的比较显示出高度的序列同一性，证实在受体-配体相互作用研究中使用p-CBRs的有效性。这种综合分析增强了对大麻素受体结构和功能动力学的理解，强调它们的生理作用和它们作为ECS内治疗靶点的潜力。
