一个内在无序的核受体的酸化调节的形态多样性和拓动力学
Vasily Akulov1,2,3, Alba Jiménez Panizo4, Eva Estébanez-Perpiñá4
1Medical Systems Biophysics and Bioengineering, Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
The journal of physical chemistry. B
|July 17, 2025
概括
葡萄糖皮质体受体N端域 (GR NTD) 的特定位点化产生了紧,纠的结构. 这揭示了酸化如何调节无序的蛋白质动力学和功能.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 固有失序蛋白 (IDP) 的特定位点酸化与蛋白质活性有关,但其对结构动态的影响仍然不太清楚.
- 人类葡萄糖皮质体受体N端域 (GR NTD),一个关键的失序蛋白质,包含一个对酸化敏感区域 (AF1c),对转录调节至关重要.
- 了解酸化如何改变IDP结构对于破译细胞信号和功能至关重要.
研究的目的:
- 调查特定位点酸化如何影响无序GR NTD的结构动态和拓.
- 阐明酸化控制GR功能和局部化的调节机制.
- 引入一种新的计算框架,用于分析无序蛋白质的拓动态.
主要方法:
- 基于电路拓学的折叠分析方法的开发.
- 野生型和化GR NTD变体的原子模拟.
- 对不同变体的拓状态 (紧与暴露于溶剂) 的比较分析.
主要成果:
- 特定地点的酸化促进非局部接触的形成,导致有显著纠的无序紧拓.
- 酸化诱导的拓变化与在暴露于溶剂状态下观察到的不同.
- 特定的酸化部位影响拓紧状态的形成,而暴露于溶剂的状态在变体中显示出类似的拓积累.
结论:
- GR NTD 的酸化通过改变蛋白质拓和动态起到复杂的调节作用.
- 这项研究引入了一种多功能分析框架,用于探索无序蛋白质的结构格局.
- 研究结果提供了关于核受体信号传输中的IDP结构功能关系的见解.
更多相关视频
相关概念视频
01:45Regulation 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
02:18Intrinsically Disordered Proteins
18.2K
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
18.2K
01:30Assembly of Signaling Complexes
5.9K
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,...
5.9K
01:22Amplifying Signals via Enzymatic Cascade
8.9K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.9K
01:34Nuclear Protein Sorting
4.8K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.8K
01:49Conserved Binding Sites
4.4K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.4K