Department of Biological Sciences, St. John's University, Queens, NY, 11439, USA.
Commun Biol. 2022 Oct 20;5(1):1110. doi: 10.1038/s42003-022-04085-2.
Otopetrin (Otop) proteins were recently found to function as proton channels, with Otop1 revealed to be the sour taste receptor in mammals. Otop proteins contain twelve transmembrane segments (S1-S12) which are divided into structurally similar N and C domains. The mechanisms by which Otop channels sense extracellular protons to initiate gating and conduct protons once the channels are activated remains largely elusive. Here we show that two extracellular loops are playing key roles in human Otop1 channel function. We find that residue H229 in the S5-S6 loop is critical for proton sensing of Otop1. Further, our data reveal that the S11-12 loop is structurally and functionally essential for the Otop1 channel and that residue D570 in this loop regulates proton permeation into the pore formed by the C domain. This study sheds light on the molecular mechanism behind the structure and function of this newly identified ion channel family.
耳石蛋白（Otop）最近被发现具有质子通道的功能，其中 Otop1 被揭示为哺乳动物的酸味受体。Otop 蛋白包含十二个跨膜片段（S1-S12），它们被分为结构相似的 N 和 C 结构域。Otop 通道感知细胞外质子以启动门控以及通道一旦被激活后传导质子的机制在很大程度上仍难以捉摸。在这里，我们表明两个细胞外环在人类 Otop1 通道功能中起着关键作用。我们发现 S5-S6 环中的残基 H229 对于 Otop1 的质子感应至关重要。此外，我们的数据揭示了 S11-12 环对于 Otop1 通道在结构和功能上是必不可少的，并且该环中的残基 D570 调节质子渗透到由 C 结构域形成的孔中。这项研究揭示了这个新鉴定的离子通道家族的结构和功能背后的分子机制。
