在ASAP1介导的Arf1 GTP水解中,一个活跃的质机制重新定义了PH域的功能功能
Olivier Soubias1,2, Samuel L Foley3, Xiaoying Jian2
1Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Nature communications
|October 1, 2025
概括
在ASAP1Pleckstrin同质域积极调节Arf1GTP水解,挑战被动膜招募模型. 这种全性机制直接调节GTPase活性,影响癌症进展和相关的上蛋白.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 激活GTPase的蛋白质 (GAPs) 调节小的GTPases.
- 一个GAP的ASAP1刺激了Arf1的GTP水解,并且与癌症有关.
- 在ASAP1的Pleckstrin同质 (PH) 域对于Arf1调节至关重要.
研究的目的:
- 研究ASAP1 PH域在Arf1 GTP水解中的作用.
- 为了确定PH域是否在膜招募之外积极调节GTPase活性.
主要方法:
- 核磁共振 (NMR) 光谱学是指核磁共振的光谱学.
- 分子动力学模拟的模拟.
- 动力测试试验 动力测试试验
- 突变分析 突变分析
主要成果:
- ASAP1 PH域在膜上积极结合Arf·GTP,诱导水解的活性状态.
- 在ASAP1 PH域和Arf1.1上都确定了调解这种全性机制的关键残留物.
- 数学建模表明,这种全性贡献对GTPase激活具有重要意义.
结论:
- PH域可以直接和积极调节小GTPase功能.
- 这种活跃的全性机制对理解Arf1调节和Ras和Rho等相关的蛋白家族具有广泛的意义.
相关概念视频
Allosteric Proteins-ATCase
6.5K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.5K
Amplifying Signals via Enzymatic Cascade
17.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
17.5K
Generation of Straight or Branched Actin Filaments
3.7K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.7K
GTPases and their Regulation
9.7K
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,...
9.7K
Small GTPases - Ras and Rho
5.2K
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:
5.2K
Activation and Inactivation of G Proteins
11.0K
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...
11.0K


