一个Arl1-ArfGEF综合体的结构洞察力,该综合体参与了Golgi招募GRIP领域的golgin
H Diessel Duan1, Bhawik K Jain2, Hua Li1
1Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Nature communications
|March 2, 2024
概括
类似Arf的1 (Arl1) 结合关氨酸核酸交换因子Gea2,稳定其二元体,并将Imh1招募到Golgi. 这种相互作用对膜贩运和戈尔吉组织至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
- 分子机制的分子机制
背景情况:
- 阿尔夫样1 (Arl1) 是一种参与戈尔吉组织的GTP结合蛋白.
- Arl1与瓜核酸交换因子Gea2相互作用,以招募golgin Imh1.1.
- Arl1-Gea2复合体也结合并激活脂胺片酶Drs2,但该机制尚不清楚.
研究的目的:
- 使用高分辨率冷电子显微镜 (cryo-EM) 阐明Arl1-Gea2相互作用的分子机制.
- 澄清Arl1结合如何影响Gea2的结构和功能.
- 了解Arl1-Gea2复合体在招募Imh1到Golgi中的作用.
主要方法:
- 高分辨率冷电子显微镜 (cryo-EM) 用于确定全长Gea2和Arl1-Gea2复合物的结构.
- 生物化学试验分析突变的相互作用界面和功能后果.
主要成果:
- 通过DCB和HUS领域的广泛相互作用,Gea2形成了一个稳定的二元体.
- Arl1与Gea2 DCB域的外部表面结合,从而保留了Gea2二次元.
- 在Arl1-Gea2相互作用接口中确定了关键残留物,包括FWY三位数和Arl1-特定的残留物.
- 破坏 Arl1-Gea2 相互作用的突变取消了 Imh1 Golgi 关联.
结论:
- 该研究提供了高分辨率结构,澄清了Arl1-Gea2相互作用机制.
- 与Gea2结合的Arl1不会破坏Gea2二聚体,这与之前的发现相反.
- 这种互动对于招募Imh1到Golgi是必不可少的,促进了对膜贩运的理解.
更多相关视频
05:43A Protein Preparation Method for the High-throughput Identification of Proteins Interacting with a Nuclear Cofactor Using LC-MS/MS Analysis
Published on: January 24, 2017
8.4K
10:19Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin
Published on: January 24, 2025
451
相关概念视频
Coat Assembly and GTPases
3.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
Rab Cascades
2.6K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.6K
Assembly of Signaling Complexes
5.8K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.8K
Rab Proteins
3.9K
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...
3.9K
GPI Anchoring of Proteins in the ER Membrane
4.1K
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
4.1K
Directing Proteins to the Rough Endoplasmic Reticulum
7.3K
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...
7.3K
