一个内部链接器和由酸丁酸5-酸盐的pH生物感知调节ESCRT-0组件TOM1的功能
Wen Xiong1, Tiffany G Roach1, Nicolas Ball2
1Protein Signaling Domains Laboratory, Department of Biological Sciences, Fralin Life Sciences Institute, and Center for Soft Matter and Biological Physics, Virginia Tech, Blacksburg, VA 24061, USA.
Structure (London, England : 1993)
|August 29, 2024
概括
Myb1 (TOM1) 的标以内体pH依赖的方式结合乌比奎丁和酸丁 5-酸盐 (PtdIns5P). 细菌感染Shigella flexneri破坏了这一过程,通过抑制蛋白质降解来帮助细菌的生存.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 传染性疾病 传染性疾病
背景情况:
- Myb1 (TOM1) 的点对于将无处不在的蛋白质运送到溶酶体以进行降解至关重要.
- 在这个过程中TOM1的调节机制还不完全理解.
- 在Shigella flexneri感染期间,TOM1充当了内体酸丁酸5- (PtdIns5P) 效应器.
研究的目的:
- 阐明调节TOM1在内体蛋白传输中的作用的机制.
- 调查PtdIns5P和pH在TOM1介导的无素蛋白降解中的作用.
- 了解Shigella flexneri感染如何影响TOM1功能和宿主细胞过程.
主要方法:
- 识别了一种与TOM1 VHS域相邻的新型DXXLL图案.
- 在TOM1 VHS域内对PtdIns5P结合基因的表征.
- 在不同pH条件下对TOM1-ubiquitin和TOM1-TOLLIP相互作用的评估.
- 在Shigella flexneri感染期间对TOM1在内体成熟中的作用的分析.
主要成果:
- 一个DXXLL基因增强了TOM1的泛素亲和力,通过酸化调节.
- TOM1在其VHS域中具有pH依赖的PtdIns5P结合基因.
- 在酸性条件下,TOM1与TOLLIP结合,但不与ubiquitin结合,而Shigella flexneri感染破坏了依赖pH的内体细胞成熟,减少了蛋白质降解.
结论:
- 姆1的乌比奎丁和PtdIns5P结合是由内体pH调节的.
- 石格拉柔性菌感染会通过改变pH依赖的TOM1信号来扰乱内体成熟.
- 这种干扰通过受损的蛋白质降解促进了细菌的生存.
关键词:
DXXLL的图案就是一个DXXLL的图案.希格拉柔性菌 (Shigella flexneri) 是一种的植物.郁金香:一个郁金香.一个TOM1TOM1一个TOM1它们是pH值依赖的.酸-5-酸盐是一种酸-5-酸-5-酸.在任何地方都是无处不在的.更多相关视频
10:52Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
Published on: January 6, 2016
10.4K
08:27Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
Published on: October 20, 2023
1.6K
相关概念视频
01:38Intralumenal Vesicles and Multivesicular Bodies
3.4K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K
01:42Phosphoinositides and PIPs
8.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K
01:28The Early Endosome: Endocytosis of Transferrin
3.2K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
3.2K
01:39Mechanism of Filopodia Formation
2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
01:11IP3/DAG Signaling Pathway
11.9K
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...
11.9K
01:45Tail-anchoring of Proteins in the ER Membrane
3.1K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K