马螺旋对α4β2nACh受体的受体组合和功能很重要
Dorottya I Fricska1, Susanne M Mesoy1, Sarah C R Lummis1
1Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Membranes
|December 22, 2023
概括
尼古丁乙胆受体 (nAChRs) 的MA螺旋中的突变会影响它们的组装和功能. 一些突变阻止受体折叠,而另一些突变允许在不开通通道的情况下结合连接体.
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
- 生物物理学的生物物理.
背景情况:
- 在神经系统中,Pentameric带离子通道 (pLGICs) 是至关重要的.
- 阴离子选择性PLGIC具有独特的MA螺旋延伸.
- 马螺旋影响受体表达和离子导电.
研究的目的:
- 研究尼古丁乙胆受体α4β2 (nAChR) 的MA区域68种突变的功能影响.
- 阐明MA螺旋在受体组合,表达和功能中的作用.
主要方法:
- 位点定向的突变发生引入68个阿拉宁突变在MA区域的α4β2nAChR.
- 使用电压敏感膜染料测量离子通道活性的功能测试.
- 放射性连接体结合测试以评估受体表达和连接体结合.
主要成果:
- 七种氨酸突变破坏了受体折叠和/或组装,功能损失和连接体结合表明.
- 两个氨酸突变允许联体结合,但取消了功能反应,表明通道关闭受损.
- 在MA螺旋中确定了对α4β2 nAChR组装和功能至关重要的特定残留物.
结论:
- 马螺旋对于α4β2nAChR的正确折叠,组装和功能至关重要.
- 在MA螺旋中的特定残留物在受体关口和连接体有效性中起着不同的作用.
- 在不同的阴离子选择性PLGIC中,MA螺旋残留的功能可能会微妙地变化.
相关概念视频
Multi-pass Transmembrane Proteins and β-barrels
5.3K
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
5.3K
Assembly of Signaling Complexes
5.8K
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,...
5.8K
Activation and Inactivation of G Proteins
7.2K
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...
7.2K
Integrins
4.0K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.0K
Transducer Mechanism: G Protein–Coupled Receptors
2.0K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
2.0K
Cholinergic Receptors: Nicotinic
2.8K
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...
2.8K


