在PAS,LOV和CRY蛋白质中保存的结构动图调节昼夜节律,是治疗点
Eric D Brinckman1, Anna E Lester1, Brian D Zoltowski1
1Department of Chemistry, Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX, 75275, USA.
FEBS letters
|February 10, 2026
概括
循环时钟使用PAS和CRY蛋白调节日常节律. 这些来自光活性祖先的蛋白质通过揭示全性机制,为各种疾病提供药物点.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 时间生物学 时间生物学
背景情况:
- 循环时钟对于调节日常生物节律至关重要,它们普遍利用周期-ARNT-单心 (PAS) 和密码色 (CRY) 蛋白质.
- 这些蛋白质经历了复杂的基因重复和功能专业化,经常保留祖先光活性蛋白的高序列身份.
研究的目的:
- 在昼夜时钟中审查PAS和CRY蛋白超级家族的结构,生化和计算研究.
- 突出它们的分子机制和作为各种疾病表型的药物点的潜力.
主要方法:
- 结构,生化和计算研究的剖析.
- 分析蛋白质-蛋白质相互作用动机和连接体结合口袋.
- 专注于光活性蛋白成员,以了解全性机制.
主要成果:
- PAS和CRY蛋白质是关键的调节者,将环境线索与昼夜节律结合起来.
- 祖先的光活性蛋白特征被重新利用为相互作用动机和药物点.
- 结合协因子与信号结合的合性机制对于昼夜调节和药物发现至关重要.
结论:
- PAS和CRY超级家族对昼夜时钟功能至关重要,并且代表治疗干预的有希望的目标.
- 了解光活性PAS/CRY蛋白质中的全性机制,可以指导治疗昼夜节律相关疾病的药物发现.
相关概念视频
Circadian Rhythms and Gene Regulation
4.6K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.6K
Conservation of Protein Domains Over Different Proteins
14.6K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.6K
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
375
Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
375
Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Covalently Linked Protein Regulators
9.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.7K
Protein and Protein Structure
88.6K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
88.6K


