对SHIP2的结构洞察力揭示了其膜调节机制
Jyoti Gupta1, Johanne Le Coq2, Daniel Lietha3
1Cell Adhesion Laboratory, UF Scripps, Jupiter, Florida, USA.
Protein science : a publication of the Protein Society
|February 12, 2026
概括
含有异醇-5酸酶2 (SHIP2) 的Src同质性2域通过去化PIP3来调节细胞功能. 它的结构揭示了域关联和膜寡合化,为SHIP2提供了洞察力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 含有异醇-5酸酶2 (SHIP2) 的Src同质2域对于酸的信号传递至关重要.
- SHIP2调节细胞功能,如增殖,粘附,迁移和生存.
- SHIP2的失调与癌症和神经退行性疾病有关,包括阿尔茨海默氏症.
研究的目的:
- 为了阐明SHIP2.2的分子机制.
- 为了确定SHIP2.2的低温电子显微镜 (cryoEM) 结构.
- 了解SHIP2的结构如何与其功能和监管有关.
主要方法:
- 低温电子显微镜 (cryoEM) 用于解决 SHIP2.2 的结构.
- 生物化学试验用于研究基质相互作用.
- 脂质相互作用研究,以调查膜关联.
主要成果:
- 冷EM结构揭示了SHIP2的斑块链同质相关域及其C2和酸酶域之间的意想不到的关联.
- 这种域排列促进了基质相互作用,特别是在更高度的酸中.
- 观察到SHIP2在细胞膜上形成寡合体.
结论:
- SHIP2的活动由其域组织和与膜脂质的相互作用来调节.
- 结构洞察力为SHIP2在各种生理和病理条件中的作用提供了机械的理解.
- 这项研究为进一步研究SHIP2向治疗奠定了基础.
关键词:
阿尔茨海默氏症的疾病是阿尔茨海默氏症.通过PI3K AKT途径进行PI3K.在PIP3中,PIP3是PIP3,PIP3是PIP3.癌症的信号传递.冰冷化EMEM可以使用.胰岛素耐药性是一种胰岛素耐药性.膜调节的调节方法神经退行症的神经退行症酸的信号传递蛋白质的寡合化.2 型糖尿病 2 型糖尿病更多相关视频
08:03Advanced Self-Healing Asphalt Reinforced by Graphene Structures: An Atomistic Insight
Published on: May 31, 2022
5.7K
13:40Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
Published on: July 7, 2011
18.7K
相关概念视频
Cis-regulatory Sequences
11.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.9K
Cis-regulatory Sequences
4.2K
4.2K
Mechanisms of Membrane-bending
3.5K
The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
3.5K
Mechanisms of Membrane Domain Formation
3.9K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.9K
Drug Absorption Mechanism: Passive Membrane Transport
7.0K
Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
7.0K
Drug Absorption Mechanism: Carrier-Mediated Membrane Transport
6.3K
Certain large, lipid-insoluble drug molecules that resemble amino acids, peptides, or glucose, require specialized carrier proteins to facilitate their diffusion across cell membranes. This transport can occur through either facilitated diffusion, which does not require energy input, or active transport, which does require energy input.
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
6.3K
