Département de Pharmacologie et de Toxicologie, Université de Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7199, Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, F-67400 Illkirch, France; Université de Strasbourg, Faculté de Pharmacie, F-67400 Illkirch, France.
J Mol Biol. 2015 Jan 16;427(1):54-66. doi: 10.1016/j.jmb.2014.06.004. Epub 2014 Jun 14.
ATP-gated P2X receptors and acid-sensing ion channels are two distinct ligand-gated ion channels that assemble into trimers. They are involved in many important physiological functions such as pain sensation and are recognized as important therapeutic targets. They have unrelated primary structures and respond to different ligands (ATP and protons) and are thus considered as two different ion channels. As a consequence, comparisons of the biophysical properties and underlying mechanisms have only been rarely made between these two channels. However, the recent determination of their molecular structures by X-ray crystallography has revealed unexpected parallels in the architecture of the two pores, providing a basis for possible functional analogies. In this review, we analyze the structural and functional similarities that are shared by these trimeric ion channels, and we outline key unanswered questions that, if addressed experimentally, may help us to elucidate how two unrelated ion channels have adopted a similar fold of the pore.
三磷酸腺苷门控 P2X 受体和酸敏离子通道是两种不同的配体门控离子通道，它们会组装成三聚体。它们参与许多重要的生理功能，如痛觉，并被认为是重要的治疗靶点。它们的一级结构没有关联，分别对不同的配体（ATP 和质子）作出响应，因此被视为两种不同的离子通道。因此，这两种通道的生物物理特性和潜在机制的比较很少被进行。然而，最近通过 X 射线晶体学确定它们的分子结构揭示了两个孔的结构上出人意料的相似之处，为可能的功能类比提供了基础。在这篇综述中，我们分析了这些三聚体离子通道所共享的结构和功能相似性，并概述了一些关键的未解决的问题，如果通过实验解决这些问题，可能有助于我们阐明两个不相关的离子通道如何采用相似的孔折叠。
