对Arp2的NPF结合与ArpC5的N端尾部的释放和Arp2/3复合体的构造变化有关
Andrew J Saks1, Kyle R Barrie1,2, Grzegorz Rebowski1
1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
概括
对于细胞移动性至关重要的Arp2/3复合体,通过核形成促进因子 (NPF) 激活. 这项研究揭示了NPF与Arp2/3复合体的结合如何诱导全变化,将其转移到为分支性actin网络形成的激活方向.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- Arp2/3复合体对于需要分支的活性蛋白网络的细胞过程至关重要,例如细胞运动.
- 它由七个子单元组成,包括与行为蛋白相关的蛋白质 (Arps) 2和3,以及五个支架子单元 (ArpC1-5).
- 该复合体存在于非活性和活性构造,激活需要诸如核化促进因子 (NPF) 等辅因子.
研究的目的:
- 阐明NPF驱动Arp2/3复杂平衡向激活的机制.
- 为Arp2/3复合体的激活过程提供高分辨率的结构洞察力.
主要方法:
- 确定了Arp2/3复合体的两个冷电子显微镜 (cryo-EM) 结构,分辨率为2.9-Å.
- 获得了与NPF结合不同子单元组合的复合体的结构 (Arp3/ArpC1与Arp3/Arp2-ArpC1).
主要成果:
- 对Arp2的NPF结合与ArpC5的N端尾部的释放和Arp2.2的形状变化有关.
- 这些形状变化包括ATP结合裂关闭和Arp2重新定位到其活性状态.
- 结合Arp3的NPF会导致其抑制性C端尾部的释放,这是之前发现的一种全效应.
结论:
- 在Arp2/3复合体上的两个NPF结合点都会诱导明显但合作的全变化.
- 这些结合的全osteric 效应集体地将该复合物的平衡转向了活跃的,分支的actin-nucleating构造.
- 了解这些机制,可以了解细胞中actin动态的调节.
相关概念视频
Generation of Straight or Branched Actin Filaments
2.8K
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...
2.8K
Regulation of Nuclear Protein Sorting
2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
GPCR Desensitization
5.7K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.7K
IP3/DAG Signaling Pathway
11.8K
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...
11.8K
Directing Proteins to the Rough Endoplasmic Reticulum
7.1K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.1K
Nuclear Protein Sorting
4.5K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.5K


