人类α10尼古丁性乙胆受体子单元组合在一起形成功能性受体
Bassel Tekarli1, Layla Azam1, Arik J Hone2
1School of Biological Sciences, University of Utah, Salt Lake City, Utah, USA.
The Journal of biological chemistry
|January 11, 2025
概括
人类α10尼古丁性乙胆受体 (nAChRs) 可以自组合成功能性同类体,独立于辅助蛋白质. 这一发现为开发选择性alpha10 nAChR配体开辟了新的途径.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 尼古丁酸乙胆受体 (nAChRs) 是关键的联结离子通道.
- 哺乳动物的nAChR包括16个子单元,允许各种异构和同构组件.
- 之前认为alpha10 nAChR亚单元需要alpha9才能发挥作用.
研究的目的:
- 为了研究人类alpha10 nAChR子单元的自我组装能力.
- 描述同质alpha10 nAChRs的功能性质.
- 确定开发alpha10 nAChR选择性药物的潜在目标.
主要方法:
- 在Xenopus卵细胞中,人类alpha10 nAChR亚单元与RIC-3的同时表达.
- 在α10子单元中引入一种功能获取突变 (V13'T).
- 电生理学记录用于测量乙胆引起的电流.
- 使用alpha-bungarotoxin,alpha-conotoxin和RgIA-5474.4进行对抗剂敏感性分析.
主要成果:
- 人类alpha10 nAChR子单元可以自组装成功能性同类体,有或没有RIC-3.
- 一个V13'T突变证实了alpha10子单元的自我组装.
- 同型α10 nAChRs与α7和α9alpha10亚型相比,具有明显的对抗剂敏感性.
- 阿尔法10同位素对阿尔法-毒素敏感,但对特定的阿尔法-毒素和RgIA-5474.4不敏感.
结论:
- 人类的alpha10 nAChR亚单元能够形成功能性的同型通道.
- 这种自我组装独立于RIC-3和strichnine.nine等辅助蛋白发生.
- 阿尔法10同类体的独特药理特征为开发选择性调节剂提供了基础.
相关概念视频
Cholinergic Receptors: Nicotinic
2.4K
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
2.4K
Cholinergic Receptors: Muscarinic
1.9K
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
1.9K
Cholinergic Neurons: Neurotransmission
2.6K
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
2.6K
Activation and Inactivation of G Proteins
6.7K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.7K
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Protein Complex Assembly
10.5K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.5K


