核受体域间通信是由带有连接体特异性的链介导的
Saurov Hazarika1, Tracy Yu2, Arumay Biswas1
1Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
Journal of molecular biology
|September 27, 2024
概括
与核受体 (如Farnesoid X受体 (FXR)) 结合的联体会导致域重组. 计算建模和实验显示,链区域对于这种域间通信至关重要.
科学领域:
- 分子生物学分子生物学
- 结构生物学是结构生物学.
- 计算化学是一种计算化学.
背景情况:
- 核受体是通过连接体结合来调节的转录因子.
- 由于在全长结构研究中的挑战,核受体中域间通信的理解较差.
研究的目的:
- 为了研究全长的Farnesoid X受体 (FXR) 的结构动力学和域间通信.
- 阐明链区域在调解带诱导的形状变化中的作用.
主要方法:
- 计算建模,包括扩展分子动力学 (>10微秒) 和增强的采样模拟.
- 蛋白质与蛋白质相互作用测试以实验验证计算发现.
主要成果:
- 干结合选择性地诱导FXR中的域重排,导致域间接触.
- 链区域在调解这些带诱导的域间接触方面发挥着至关重要的作用.
- 计算和实验数据揭示了FXR结构和功能的新方面.
结论:
- 在FXR中,联结体诱导的域间通信涉及由链区域介导的特定域重排.
- 这项研究为表征其他全长核受体提供了一个框架.
更多相关视频
09:07Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
6.3K
11:07Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
16.4K
相关概念视频
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Internal Receptors
69.6K
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
69.6K
Signal Transduction: Overview
8.3K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
8.3K
Types of Receptors: Internal Receptors
23.1K
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
23.1K
Intracellular Hormone Receptors
55.1K
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
55.1K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
