伊拉克-M死亡领域:一个三面的故事
Berke Gürkan1,2, Hessel Poelman3,4, Liza Pereverzeva1,2
1Center of Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.
Frontiers in molecular biosciences
|January 25, 2024
概括
介素-1受体关联激酶-M (IRAK-M) 通过其死亡域 (DD) 通过特定的表面激活NF-κB. 剩余的Arg97是NF-κB激活和相互作用的关键,影响炎症信号通路.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 介素-1受体关联激酶-M (IRAK-M) 是一种抗炎蛋白,可以负面调节MyD88/IRAK-4/IRAK-1信号传输.
- 已经证明IRAK-M通过MyD88/IRAK-4/IRAK-M基因组以MEKK-3依赖的方式激活NF-κB.
研究的目的:
- 阐明IRAK-M激活NF-κB的结构机制.
- 为了确定参与NF-κB激活和蛋白相互作用的IRAK-M死亡域 (DD) 的特定残留物和表面.
主要方法:
- IRAK-M死亡域 (DD) 残留物的位点定向突变发生.
- 在具有特定IRAK-M突变和淘汰的细胞中分析NF-κB激活.
- 对IRAK-M寡合化的结构建模.
主要成果:
- 伊拉克-M利用其DD的三个表面来激活MyD88/IRAK-4/IRAK-M下游的NF-κB.
- 表面1 (Trp74) 结合了MyD88/IRAK-4;表面2 (Lys60) 促进了IRAK-M同位素的形成.
- 表面3 (Arg97) 对于NF-κB激活 (50%的贡献),IRAK-1相互作用和TRAF6相互作用至关重要,即使没有直接的MyD88/IRAK-4结合.
结论:
- 伊拉克-M DD四聚合物,特别是Arg97表面,通过与IRAK-1和TRAF6.6的相互作用促进NF-κB的激活.
- 结构建模表明IRAK-M homo-octamer形成,解释了Arg97突变如何通过与IRAK-1结合竞争来增强抑制性质.
- 伊拉克-M的结构功能特性突显了其作为炎症疾病治疗点的潜力.
相关概念视频
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
Overview of Cell Death
7.3K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.3K
Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
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
Equipotential Surfaces and Field Lines
3.8K
Electric potential can be pictorially represented as a three-dimensional surface. On such a surface, the electric potential is constant everywhere. The equipotential surface is always perpendicular to the electric field lines, and while it is three-dimensional, it can be treated as an equipotential line in a two-dimensional case. These equipotential lines are also always perpendicular to electric field lines. The term equipotential is often used as a noun, referring to an equipotential line or...
3.8K
The Inner Mitochondrial Membrane
3.4K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.4K


