所有ras蛋白都是多聚烯基的,但只有部分是棕基基的
J F Hancock1, A I Magee, J E Childs
1Section of Cell and Molecular Biology, Royal Cancer Hospital, Chester Beatty Laboratories, London, England.
Cell
|June 30, 1989
概括
拉斯蛋白在它们的C端氨酸上经过多烯化. 棕化发生在其他地方,增强膜结合和转化活性,这对生物功能至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 拉斯蛋白是关键的信号分子,参与细胞生长和分化.
- 翻译后的修改,包括前化和棕化,对Ras功能至关重要.
- 以前的理解表明,棕化发生在Ras蛋白的C端半氨酸上.
研究的目的:
- 阐明聚烯化和棕化在Ras蛋白功能的确切位置和作用.
- 调查这些修改对Ras膜协会和生物活性的影响.
主要方法:
- 利用突变分析来识别参与棕代谢的氨酸残留物.
- 研究了改性Ras蛋白的生物活性和膜关联.
- 评估了抑制聚伊索胺生物合成对Ras膜局部化的影响.
主要成果:
- 所有的Ras蛋白都在Cys186.6上被多化.
- 棕化发生在超变域内的氨酸残留物上,而不是Cys186.6.
- 聚伊索普里尼化但非棕化H-ras是活跃的,并且与膜有很弱的关联.
- 棕化增强了膜结合力和转化活性.
- 抑制聚伊索胺合成取消了Ras膜协会.
结论:
- 对Cys186的多烯化对Ras生物活性和膜协会至关重要.
- 棕化发生在明显的氨酸残留物上,调节了膜结合和转化功效.
- 这些发现完善了对Ras翻译后修改及其功能后果的理解.
相关概念视频
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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...
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...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
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...
Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.


