通过腺二酸盐核糖和激活TRPM2通道的演化轨迹
Cheng Ma1, Yanping Luo2, Congyi Zhang2
1Department of Biophysics and Department of Neurosurgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Protein Facility, Core Facilities, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.
Science bulletin
|May 11, 2024
概括
TRPM2离子通道的演变
科学领域:
- 分子生物学分子生物学
- 进化生物学是进化的生物学.
- 生物化学 生物化学
背景情况:
- 带离子通道对于生物过程至关重要.
- 通过腺二酸核糖 (ADPR) 和激活TRPM2 (过时受体潜在梅拉斯塔丁2) 离子通道,随着时间的推移而演变.
- TRPM2门的进化轨迹在很大程度上仍未被探索.
研究的目的:
- 在各种动物物种中研究TRPM2门机制的分子进化.
- 阐明TRPM2.2在连接体结合和敏感性的进化转变.
- 识别出新的关模式,填补TRPM2的进化历史上存在的空白.
主要方法:
- 进行了来自280多种动物的TRPM2序列的分子进化分析.
- 研究了NUDT9-H和MHR领域的进化变化.
- 分析了TRPM2通道内结合部位的演变.
主要成果:
- C终端的NUDT9-H域从酶功能演变为激活的联体结合部位.
- 在整个进化过程中,N端的MHR域保留了一个保留的连接结位.
- 门从早期物种的单一结合部位演变为包括人类在内的脊椎动物的多个部位.
- 发现了一种具有独特关门模式的新型TRPM2组 (olTRPM2),弥合了进化差距.
结论:
- 在过去的10亿年里,TRPM2连接体结合和激活模式经历了至少三个不同的阶段,从简单的发展到复杂和协调的机制.
- 这些发现提供了关于离子通道关的进化途径的见解.
- 这项研究为了解其他通道蛋白的进化提供了一个框架.
相关概念视频
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Feedback Regulation of Calcium Concentration
3.4K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.4K
IP3/DAG Signaling Pathway
12.0K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.0K
Amplifying Signals via Second Messengers
6.9K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
6.9K
G-Protein Gated Ion Channels
4.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.6K
What are Second Messengers?
83.6K
Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
83.6K


