细胞内膜网膜PI(3) P脂质结合的目标是疟疾蛋白质与宿主细胞结合
Souvik Bhattacharjee1, Robert V Stahelin, Kaye D Speicher
1Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA.
Cell
|January 24, 2012
概括
疟疾寄生虫Plasmodium falciparum使用宿主向 (HT) 信号来输出蛋白质. 这种信号被内细胞网膜中的酸-3-酸盐 (PI(3) P) 识别,独立于蛋白质酶裂变,揭示了一条新的分泌途径.
科学领域:
- * 分子生物学 * 分子生物学
- * 寄生虫学 寄生虫学
- * 细胞生物学 细胞生物学
背景情况:
- * 疟疾寄生虫Plasmodium falciparum通过宿主向 (HT) 信号出口了数百种效应蛋白.
- *以前认为出口仅取决于ER蛋白酶,等离子素V的裂变.
- *了解Plasmodium falciparum分泌对于开发新的抗疟疾策略至关重要.
研究的目的:
- * 调查Plasmodium falciparum中HT信号介导蛋白质出口的机制.
- * 确定酸盐酸-3- (PI(3) P) 在蛋白质分泌中的作用.
- * 探索这种出口机制在其他病原体中的保存.
主要方法:
- *分析HT信号与酸盐酸-3-酸盐 (PI(3) P) 的结合.
- * 显微镜可可视化寄生虫内 плазма网膜 (ER) 内的PI(3) P和HT信号.
- * 对Plasmodium falciparum和一种致病性菌体的HT信号输出进行比较分析.
主要成果:
- *HT信号直接与PI(3) P结合,具有很高的亲和力,独立于等离子素V裂变.
- *在ER中的PI(3) P富含区域与出口前体的HT信号进行局部化.
- *依赖PI(3) P的出口被保存在相关的致病性菌体中,即使没有等离子素V.
结论:
- * ER中的酸-3-酸盐 (PI(3) 是HT信号驱动蛋白质出口的关键媒介.
- * 这种PI(3) P识别机制在蛋白酶作用之前,并且独立于蛋白酶作用.
- *这些发现揭示了对Plasmodium falciparum和其他生物体的致病性至关重要的保存分泌途径.
相关概念视频
Phosphoinositides and PIPs
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...
Lipids as Anchors
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the...
Directing Proteins to the Rough Endoplasmic Reticulum
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...
IP3/DAG Signaling Pathway
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 produces two-second...
GPI Anchoring of Proteins in the ER Membrane
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,...
Rab Proteins
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...


