GTP水解触发了AMPH-1的膜重塑.
Wei Gai1, Yuhang Wang1, Brianna Martin1
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77845, USA.
Science advances
|August 1, 2025
概括
两素蛋白AMPH-1通过结合和化关氨酸核酸驱动运输载体的形成. 这一过程涉及膜管道和晶格形成,对于将分子返回细胞表面至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 膜贩卖 膜贩卖 膜贩卖
背景情况:
- 膜封闭的运输载体介导分子从循环内分体回归到等离子体膜.
- 载体形成的精确机制仍然不完全理解.
- 在Caenorhabditis elegans中,安菲素 (AMPH-1) 对于循环内分泌体的载体生物发生是必不可少的.
研究的目的:
- 阐明AMPH-1促进运载体形成的分子机制.
- 提出并测试一种模型,将关氨酸核酸结合和水解与AMPH-1的膜重塑功能联系起来.
- 了解AMPH-1在膜管道和囊泡中的结构动态的作用.
主要方法:
- 使用纯化的AMPH-1和脂质体进行生物化学测试.
- 研究AMPH-1与不同关氨酸核酸结合状态 (GTP与GDP) 的膜相互作用.
- 对AMPH-1在膜管道和寡合化中的作用的结构分析.
主要成果:
- 纯化的AMPH-1单独可以诱导脂质体的管管和囊泡.
- 关氨酸核酸结合调节AMPH-1的膜结合和结构转变.
- 结合GTP可通过N端的两螺旋稳定AMPH-1膜相互作用.
- 与GDP结合的AMPH-1形成了一个寡合格子,该格子管状膜,在裂变之前.
结论:
- 提出了一个模型,其中GTP结合和水解驱动AMPH-1-介导膜重塑以形成载体.
- 由瓜核酸调节的AMPH-1的构造变化,对于组织运输所需的膜结构至关重要.
- 这项研究提供了关于两素在内体循环和膜贩运中的作用的机制性见解.
相关概念视频
IP3/DAG Signaling Pathway
12.4K
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...
12.4K
Activation and Inactivation of G Proteins
7.7K
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...
7.7K
Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
Small GTPases - Ras and Rho
4.2K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.2K
Rab Proteins
4.1K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.1K
GTPases and their Regulation
8.6K
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,...
8.6K


