5-HT3 receptor subtypes: functional and structural characterisation

5-HT3 受体亚型：功能和结构表征

• 批准号: MR/L021676/1
• 负责人: Sarah Lummis
• 金额: $ 94.15万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL021676%2F1
• 关键词: HT3; receptor; subtypes; functional; structural

5-HT3 receptors are membrane protein which transmit information in the nervous system. They are also the target of many drugs. They are, for example, the 'gold standard' for treatment of postoperative and chemotherapy- and radiotherapy-induced nausea and vomiting, and studies have revealed many potential disease targets that might be amenable to alleviation by 5-HT3 receptor-selective compounds; these include chronic heart pain, bulimia, addiction, pruritis, emesis, fibromyalgia, migraine, rheumatic diseases and neurological phenomena such as anxiety and cognitive function. The receptors are constituted of 5 subunits, some of which have been associated with specific disorders, but the composition and properties of receptors composed of multiple subunits have not yet been studied. To understand how alterations in these subunits could cause disorders, and to provide a template for novel therapeutic agents that could act at complex 5-HT3 receptors, it is essential to determine the properties of these as yet uncharacterised receptors. This is the aim of this project.

5-HT 3受体是神经系统中传递信息的膜蛋白。它们也是许多药物的目标。例如，它们是治疗手术后和化疗和放疗引起的恶心和呕吐的“金标准”，并且研究已经揭示了许多潜在的疾病靶点，这些靶点可能适合于通过5-HT 3受体选择性化合物来缓解;这些疾病包括慢性心脏疼痛、贪食症、成瘾、神经炎、呕吐、纤维肌痛、偏头痛风湿性疾病和神经现象，如焦虑和认知功能。受体由5个亚基组成，其中一些与特定疾病有关，但由多个亚基组成的受体的组成和性质尚未研究。为了了解这些亚基的改变如何导致疾病，并为可以作用于复杂5-HT 3受体的新型治疗剂提供模板，必须确定这些尚未表征的受体的特性。这就是这个项目的目的。

项目成果

A Single Mutation in the Outer Lipid-Facing Helix of a Pentameric Ligand-Gated Ion Channel Affects Channel Function Through a Radially-Propagating Mechanism.

• DOI: 10.3389/fmolb.2021.644720
• 发表时间: 2021
• 期刊: Frontiers in molecular biosciences
• 影响因子: 5
• 作者: Crnjar A;Mesoy SM;Lummis SCR;Molteni C
• 通讯作者: Molteni C

Crotonic Acid Blocks the $\textit{Gloeobacter}$ Ligand-Gated Ion Channel (GLIC) via the Extracellular Domain.

巴豆酸通过细胞外结构域阻断 $ extit{Gloeobacter}$ 配体门控离子通道 (GLIC)。

• DOI: 10.17863/cam.6659
• 发表时间: 2016
• 作者: Alqazzaz M

5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems.

• DOI: 10.1021/acschemneuro.5b00080
• 发表时间: 2015-07-15
• 期刊: ACS chemical neuroscience
• 影响因子: 5
• 作者: Corradi J;Thompson AJ;McGonigle I;Price KL;Bouzat C;Lummis SC
• 通讯作者: Lummis SC

The Proton Responsiveness in the Extracellular Domain of GLIC Differs in the Presence of the ELIC Transmembrane Domain

• DOI: 10.1021/acs.biochem.6b00900
• 发表时间: 2017-04-18
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Alqazzaz, Mona A.;Price, Kerry L.;Lummis, Sarah C. R.
• 通讯作者: Lummis, Sarah C. R.