Pentameric ligand-gated ion channels (pLGICs) and their lipid microenvironments appear to have acquired mutually adaptive traits along evolution: 1) the three-ring architecture of their transmembrane (TM) region; 2) the ability of the outermost TM ring to convey lipid signals to the middle ring, which passes them on to the central pore ring, and 3) consensus motifs for sterol recognition in all pLGICs. Hopanoids are triterpenoid fossil lipids that constitute invaluable biomarkers for tracing evolution at the molecular scale. The cyanobacterium Gloeobacter violaceus is the oldest known living organism in which the X-ray structure of its pLGIC, GLIC, reveals the presence of the above attributes and, as discussed in this review, the ability to bind hopanoids. ELIC, the pLGIC from the bacillus Erwinia chrysanthemi is the only other known case to date. Both prokaryotes lack cholesterol but their pLGICs exhibit the same sterol motifs as mammalian pLGIC. This remarkable conservation suggests that the association of sterols and hopanoid surrogate molecules arose from the early need in prokaryotes to stabilize pLGIC TM regions by means of relatively rigid lipid molecules. The conservation of these phenotypic traits along such a long phylogenetic span leads us to suggest the possible co-evolution of these sterols with pLGICs.

五聚体配体门控离子通道（pLGIC）及其脂质微环境似乎在进化过程中获得了相互适应的特征：1）它们的跨膜（TM）区的三环结构；2）最外层TM环将脂质信号传递至中环的能力，该信号将其传递至中心孔环，以及3）所有pLGIC中固醇识别的共有基序。Hopanoids是三萜类化石脂质，构成了在分子规模上追踪进化的宝贵生物标记。蓝藻紫球藻是已知的最古老的活生物体，其pLGIC GLIC的X射线结构揭示了上述属性的存在，并且，如本综述所讨论的，其具有结合类胡萝卜素的能力。ELIC，来自细菌的pLGIC菊花欧文氏菌是迄今为止唯一已知的其他病例。两种原核生物都缺乏胆固醇，但它们的pLGIC与哺乳动物pLGIC表现出相同的固醇基序。这种显着的保守性表明，固醇和类胡烷替代物分子之间的联系源于对原核生物的早期需求，即通过相对刚性的脂质分子来稳定pLGIC TM区域。在如此长的系统发育跨度中这些表型性状的保守性使我们建议这些固醇与pLGICs可能共同进化。