Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography. The tetrameric structures have near-symmetric transmembrane domains, and asymmetric extracellular domains, and can bind serotonin molecules. Computer simulations, based on our cryo-EM structures, were used to decipher the assembly pathway of pentameric 5-HT3R and suggest a potential functional role for the tetrameric receptors.

中文翻译：

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血清素门控的 5-HT3A 受体离子通道的四聚体形式的结构。


多聚体膜蛋白在内质网中产生并运输到其靶膜，对于离子通道，通常是质膜。尽管有许多完全组装的通道结构可用，但我们对组装中间体、多聚体组装机制和非标准组装的潜在功能的理解是有限的。我们证明五聚体配体门控血清素 5-HT3A 受体 （5-HT3AR） 可以组装成四聚体形式，并使用冷冻电子显微镜和断层扫描报告细胞衍生微泡质膜和膜模因学中四聚体的结构。四聚体结构具有近乎对称的跨膜结构域和不对称的细胞外结构域，并且可以结合 5-羟色胺分子。基于我们的冷冻电镜结构的计算机模拟用于破译五聚体 5-HT3R 的组装途径，并表明四聚体受体的潜在功能作用。