酸化RyR2同时扩大二并重新排列四聚合物
Parisa Asghari1, David R L Scriven1, Saba Shahrasebi1
1Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
The Journal of general physiology
|February 22, 2024
概括
氨酸受体 (RyR2) 的酸化直接影响其结构和功能. 特定突变和β-上腺刺激揭示了RyR2四聚体排列对于细胞反应至关重要.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 细胞生物物理学 细胞生物物理学
背景情况:
- 第二种类型的氨酸受体 (RyR2) 对于心肌细胞中的释放至关重要.
- 之前的研究表明,RyR2四分体在酸化后重新排列,但RyR2酸化的直接作用尚不清楚.
研究的目的:
- 调查RyR2酸化状态对其结构组织和功能的直接影响.
- 阐明特定RyR2化位点 (S2030,S2808,S2814) 在对β-上腺刺激的反应中的作用.
主要方法:
- 使用了具有特定RyR2突变 (S2030A,S2808A,S2814A,S2814D) 的基因工程小鼠.
- 采用传输电子显微镜 (TEM) 和双倾斜电子断层扫描来可视化RyR2分布和二结构.
- 在β-激动剂 (异二醇) 刺激后测量功能反应.
主要成果:
- 仅仅S2814D突变就诱导了双扩张和RyR2四分体重组,这表明酸化和微型架构之间存在直接联系.
- 异二醇在S2808A,S2814A和野生型小鼠中引起了二扩张,但不是S2030A突变.
- S2030和S2808的酸化部位对于完全的β-上腺素反应至关重要,而S2814在功能上不那么重要.
- 突变差异性地影响了RyR2四聚合物阵列组织,结构变化与功能结果相关.
结论:
- RyR2酸化状态直接影响其微观结构,包括二大小和四聚体排列.
- 在RyR2数组中的四体-四体接触具有功能意义.
- 由β-上腺素受体激动剂对RyR2结构的动态改变与通道功能有关.
相关概念视频
Phosphorylation
50.3K
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...
50.3K
Receptor Tyrosine Kinases
12.9K
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...
12.9K
Enzyme-linked Receptors
78.4K
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...
78.4K
Protein Kinases and Phosphatases
13.1K
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...
13.1K
Mechanism of Filopodia Formation
2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
The Contractile Ring
6.4K
Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...
6.4K


