综合性方法揭示了rPTPε和-Src复合体形成的远端碰撞点
Nadendla EswarKumar1, Cheng-Han Yang2, Sunilkumar Tewary3
1Institute of Biological Chemistry, Academia Sinica, 128 Academia Road Sec. 2, Nankang, Taipei 115, Taiwan; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Structure (London, England : 1993)
|October 5, 2023
概括
由于短暂的相互作用,很难确定蛋白氨酸酸酶 (PTP) 复杂结构. 一个整合性的工作流程模拟了这些相互作用,揭示了PTP功能和特异性的关键见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子动力学分子动力学
背景情况:
- 确定蛋白氨酸酸酶 (PTP) 和蛋白复合物的结构对于理解氨基酸水平的特异性至关重要.
- 结合相互作用的短暂性质对传统的结构生物学技术,如蛋白质结晶学和冷电子显微镜 (cryoEM) 提出了重大挑战.
研究的目的:
- 建立一个整合性工作流程来建模过渡性蛋白质:-蛋白质复合体.
- 描述rPTPεD1和光-SrcKD之间的短暂蛋白质-蛋白质相互作用.
主要方法:
- 使用了一个包含rPTPεD1和-SrcKD的模型系统.
- 采用了一个整合性工作流程,结合了预先确定的蛋白质结构,小角度X射线散射 (SAXS) 和pTyr定制的分子动力学 (MD) 模拟.
- 进行实验验证,包括对关联率和接口突变影响的测量.
主要成果:
- 生成了rPTPεD1:-SrcKD复合物的可靠模型,揭示了短暂的蛋白质-蛋白质相互作用.
- 实验验证证证实了模拟的短暂相互作用.
- 复杂接口的突变破坏了短暂的相互作用,降低了关联率和酸酶活性.
结论:
- 开发的综合性方法成功地模拟了PTP:蛋白-蛋白质复合体中的短暂蛋白质-蛋白质相互作用.
- 这种方法广泛适用于研究其他PTP复合体和表征短暂的蛋白质-蛋白质接口.
- 了解这些短暂的相互作用是阐明PTP功能和特异性的关键.
相关概念视频
Receptor Tyrosine Kinases
13.1K
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...
13.1K
Directing Proteins to the Rough Endoplasmic Reticulum
7.3K
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...
7.3K
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
Phosphoinositides and PIPs
8.6K
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...
8.6K


