Structure of tetrameric forms of the serotonin-gated 5-HT3A receptor ion channel.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
EMBO Journal Pub Date : 2024-10-01 Epub Date: 2024-09-04 DOI:10.1038/s44318-024-00191-5
Bianca Introini, Wenqiang Cui, Xiaofeng Chu, Yingyi Zhang, Ana Catarina Alves, Luise Eckhardt-Strelau, Sabrina Golusik, Menno Tol, Horst Vogel, Shuguang Yuan, Mikhail Kudryashev
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引用次数: 0

Abstract

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.

羟色胺门控 5-HT3A 受体离子通道的四聚体结构。
多聚膜蛋白在内质网中产生,并被运输到其目标膜上,对于离子通道来说,目标膜通常是质膜。尽管有许多完全组装的通道结构,但我们对组装中间体、多聚体组装机制以及非标准组装的潜在功能的了解还很有限。我们证明了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,并利用冷冻电镜和断层扫描技术报告了细胞衍生微囊质膜和膜记忆体中的四聚体结构。四聚体结构具有近乎对称的跨膜结构域和不对称的胞外结构域,并能与血清素分子结合。根据我们的冷冻电镜结构进行的计算机模拟破解了五聚体 5-HT3R 的组装途径,并提出了四聚体受体的潜在功能作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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