对于EGFR柔膜域的膜结合的结构决定因素
Ziwei Wu1,2, Ling Li3, Lina Zhu1,2
1High Magnetic Field Laboratory, CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.
FEBS letters
|April 8, 2024
概括
表皮生长因子受体 (EGFR) 柔膜域 (JM) 特别与某些细胞膜结合,影响其活性. 这种膜相互作用部位可能调节EGFR二分化和致癌激酶激活.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 表皮生长因子受体 (EGFR) 的过度活化驱动多种癌症.
- EGFR柔膜域 (JM) 与细胞膜相互作用,调节激酶活性.
- 由EGFR-JM识别的特定脂质和相互作用细节尚未得到充分理解.
研究的目的:
- 阐明EGFR-JM的脂质识别特异性.
- 描述EGFR-JM和膜相互作用的分子细节.
- 研究膜结合对EGFR活性的功能影响.
主要方法:
- 用脂质条和脂质体拉下测试来确定特定的脂质相互作用.
- 基于NMR定位的化学转移扰动和偏磁放松增强分析被用于绘制膜结合部位的地图.
- 生物信息分析预测了JM区域内的二元化动机.
主要成果:
- EGFR-JM特别结合含有酸丁酸4,5-双酸盐 (PI(4,5) P2) 或酸丁氨酸的膜.
- 膜结合部位被映射到JM域内的Isoleucine 649到Leucine 659 (I649L659) 的残留物.
- 这种已识别的膜结合区域与JM域的预测二分化模式 (655LRRLL659) 重叠.
结论:
- EGFR-JM表现出特定的脂质识别,与PI{4,5) P2和含酸胺的膜相互作用.
- 已经证明了对JM域的膜结合,涉及I649L659残留物.
- 膜结合部位与二分化动机的接近表明,膜相互作用可能调节EGFR JM二分化和随后的激酶激活,为EGFR驱动的癌症提供潜在的治疗点.
相关概念视频
Mechanisms of Membrane Domain Formation
3.0K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.0K
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
Lipids as Anchors
5.6K
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 carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
5.6K
GPI Anchoring of Proteins in the ER Membrane
4.0K
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,...
4.0K
Membrane Domains
5.4K
The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
5.4K
Multi-pass Transmembrane Proteins and β-barrels
5.3K
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
5.3K


