Drk-SH2域的结构和动力学及其与Sev受体氨酸激酶的特定位点相互作用
Pooppadi Maxin Sayeesh1, Mayumi Iguchi1, Kohsuke Inomata1
1Department of Chemistry, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan.
International journal of molecular sciences
|June 27, 2024
概括
这项研究揭示了Drosophila下游受体激酶 (Drk) SH2域的3D结构,这对于信号传导至关重要. 这提供了关于Drk如何与细胞信号通路中的受体氨酸激酶相互作用的见解.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 德洛索菲拉下游受体激酶 (Drk) 是人类GRB2的同类物,在细胞内信号转导中发挥关键作用.
- Drk通过其Src同质2 (SH2) 域与受体氨酸激酶 (RTKs) 上的酸化氨酸残留物结合来调解信号.
研究的目的:
- 为了确定Drk SH2域 (Drk-SH2) 的溶液NMR结构.
- 为了阐明Drk-SH2与来自Sevenless (Sev) RTK的含酸 (pY) 的酸之间的特定相互作用.
- 分析-联体复合体的动态和方向.
主要方法:
- 使用溶液核磁共振 (NMR) 谱学来确定Drk-SH2.2的3D结构.
- 进行了NMR定位实验,以绘制相互作用地点的地图.
- 用NMR放松实验和分子动力学模拟来研究Drk-SH2的动力学.
- 使用对接模拟来预测的方向.
主要成果:
- Drk-SH2的溶液结构呈现出典型的SH2域折叠,其中有三个β链和两个α螺旋.
- 确定了Drk-SH2和pY-之间的特定位点相互作用.
- 描述了Drk-SH2的动态,并通过分子动态模拟提供了对其灵活性的见解.
- 对接模拟显示了与实验数据和同类蛋白质一致的基导向.
结论:
- 确定的结构和相互作用分析提供了对RTK信号传递中的Drk-SH2功能的详细分子理解.
- 这些发现提供了对跨物种SH2域相互作用的保存机制的见解.
- 这些结构和动态信息对于理解涉及Drk和GRB2同类物体的信号传导途径是有价值的.
相关概念视频
Receptor Tyrosine Kinases
12.7K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
12.7K
Assembly of Signaling Complexes
5.7K
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,...
5.7K
Transducer Mechanism: Enzyme-Linked Receptors
2.4K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.4K
Conservation of Protein Domains Over Different Proteins
10.8K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K
Enzyme-linked Receptors
78.0K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
78.0K
The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K


