不典型的双重特异性酸酶中的内在无序区域:一篇综述
Diana R D C G Pacheco1, Sofia F Forti1, Fabio L Forti1
1Laboratory of Signaling in Biomolecular Systems, Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Brazil.
International journal of biological macromolecules
|September 1, 2025
概括
在非典型的双特异性酸酶 (ADUSP) 中,内在无序区域 (IDR) 提供了细胞信号的动态调节. 了解它们的形状可塑性和相互作用是开发癌症和神经退行症新疗法的关键.
科学领域:
- 生物化学和分子生物学
- 细胞信号传输
- 结构生物学
背景情况:
- 内在无序区域 (IDR) 对于细胞适应性和快速反应至关重要.
- 在蛋白质氨酸酸酶 (PTP),特别是双特异性酸酶 (DUSP) 中,IDRs发挥着积极的功能作用.
- 非典型的DUSP (ADUSP) 利用IDR进行基质招募,自抑制和MAPK通路调节,通过后翻译修饰 (PTM) 实现信号整合.
研究的目的:
- 调查PTM如何影响DUSP IDR的结构和活动.
- 探索针对癌症和神经退行等疾病的IDR介导相互作用的治疗潜力.
- 确定DUSPIDR在应力下是否形成相隔信号复合体.
主要方法:
- 多学科方法包括冷电磁,NMR,SAXS,smFRET,计算建模,CD,SEC-MALS,HDX-MS和LiP-MS.
- 技术侧重于阐明瞬态构造,蛋白质动力学和相互作用网络.
- 使用结构和生物物理方法来理解IDR的功能.
主要成果:
- ADUSP使用IDR进行关键的调节功能,包括基质结合和路径调节.
- PTM被确定为DUSPIDR结构和功能的关键调节器.
- 这项研究强调了IDRs在细胞信号和疾病中的动态性质.
结论:
- 在ADUSP中,IDR调节为了解细胞信号提供了一个新的范式.
- 针对IDRs的形状可塑性提供了一个有前途的治疗途径,超出了传统的活性位点抑制.
- 进一步研究IDR的动态和相互作用可能会彻底改变复杂疾病的治疗方法.
相关概念视频
Protein Kinases and Phosphatases
13.4K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.4K
Intrinsically Disordered Proteins
18.1K
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...
18.1K
Phosphorylation
51.1K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
51.1K
Assembly 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
Phosphoinositides and PIPs
8.7K
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...
8.7K
Allosteric Proteins-ATCase
5.9K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.9K


