Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature. 2023 Apr;616(7956):373-377. doi: 10.1038/s41586-023-05822-1. Epub 2023 Apr 12.
Chemotactile receptors (CRs) are a cephalopod-specific innovation that allow octopuses to explore the seafloor via 'taste by touch'. CRs diverged from nicotinic acetylcholine receptors to mediate contact-dependent chemosensation of insoluble molecules that do not readily diffuse in marine environments. Here we exploit octopus CRs to probe the structural basis of sensory receptor evolution. We present the cryo-electron microscopy structure of an octopus CR and compare it with nicotinic receptors to determine features that enable environmental sensation versus neurotransmission. Evolutionary, structural and biophysical analyses show that the channel architecture involved in cation permeation and signal transduction is conserved. By contrast, the orthosteric ligand-binding site is subject to diversifying selection, thereby mediating the detection of new molecules. Serendipitous findings in the cryo-electron microscopy structure reveal that the octopus CR ligand-binding pocket is exceptionally hydrophobic, enabling sensation of greasy compounds versus the small polar molecules detected by canonical neurotransmitter receptors. These discoveries provide a structural framework for understanding connections between evolutionary adaptations at the atomic level and the emergence of new organismal behaviour.
化学机械感受器（CR）是头足类动物特有的创新结构，使章鱼能够通过“触摸味觉”来探索海底。CR 从烟碱型乙酰胆碱受体分化而来，介导不溶性分子的接触依赖性化学感觉，这些分子在海洋环境中不易扩散。在这里，我们利用章鱼 CR 来探索感觉受体进化的结构基础。我们展示了章鱼 CR 的低温电子显微镜结构，并将其与烟碱型受体进行比较，以确定能够进行环境感知与神经传递的特征。进化、结构和生物物理分析表明，参与阳离子渗透和信号转导的通道结构是保守的。相比之下，正位配体结合位点受到多样化选择的影响，从而介导对新分子的检测。低温电子显微镜结构中的偶然发现表明，章鱼 CR 的配体结合口袋具有异常的疏水性，能够感知油腻化合物，而不是经典神经递质受体检测到的小极性分子。这些发现为理解原子水平的进化适应与新的生物行为出现之间的联系提供了结构框架。
