在一个古老的TRPM chanzyme及其分子进化中的合酶活性和关
Yihe Huang1,2, Sushant Kumar1, Junuk Lee1
1Van Andel Institute, Grand Rapids, MI, USA.
Nature structural & molecular biology
|May 21, 2024
概括
这项研究揭示了TRPM2酶如何使用缓慢的ADP-ribose水解来调节自身的门. 这种自我调节机制涉及酶四化用于通道开放和水解用于关闭.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 道酶是具有酶功能的离子通道.
- TRPM2酶组合了道活性与ADP-ribose水解.
- 了解它们的综合功能至关重要.
研究的目的:
- 调查来自类鞭毛体的TRPM2酶.
- 阐明道关与酶活性之间的合机制.
- 确定NUDT9-H域的进化轨迹.
主要方法:
- 时间分辨率低温电子显微镜 (tr-cryo-EM).
- 关门和催化循环的结构分析.
- 生物化学试验用于研究酶动力学和进化.
主要成果:
- 捕获了完整的门和催化周期的结构快照.
- 已证明ADP-ribose结合会触发NUDT9-H四重化和通道开放.
- 显示的缓慢水解降低了局部ADP-ribose,诱导通道关闭,揭示了自我调节.
- 追踪了NUDT9-H域从半独立到集成的门关组件的演变.
结论:
- NUDT9-H模块的缓慢动力学为TRPM2酶提供了一个独特的自我调节机制.
- 随着NUDT9-H域的进化,它在先进物种中成为通道激活的关键.
- 结构洞察力揭示了酶活性和离子通道关之间的复杂相互作用.
相关概念视频
Mechanically-gated Ion Channels
6.4K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
6.4K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.2K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.2K
Introduction to Mechanisms of Enzyme Catalysis
8.1K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
8.1K
Activation and Inactivation of G Proteins
7.0K
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...
7.0K
GTPases and their Regulation
8.3K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.3K
Transducer Mechanism: Enzyme-Linked Receptors
2.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.4K


