酸化机制切换胺激酶是快速蛋白质进化的工具:来自AlphaFold模型的见解
Federico A Olivieri1,2, Marcelo A Marti1,2, Diana E Wetzler1,2
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Ciudad de Buenos Aires, Argentina.
Proteins
|June 17, 2024
概括
丁激酶 (HKs) 使用 cis 或 trans 酸化机制,由螺旋长度决定. 阿尔法模型揭示了这些机制是常见的和进化的,帮助细菌信号通路的特异性.
科学领域:
- 细菌信号和两个组件系统.
- 蛋白质的结构和功能.
- 进化生物学是进化的生物学.
背景情况:
- 胺激酶 (HKs) 对于细菌感知和响应环境变化至关重要.
- HKs是多域蛋白质,它们作为同位体起作用,利用cis或trans自酸化机制来实现通路特异性.
- 这些独特的酸化机制的结构和进化基础仍然不清楚.
研究的目的:
- 通过计算建模,研究HKs中cis与trans自酸化的结构决定因素.
- 分析HKs中cis和trans酸化机制的进化流行和历史.
- 探索HK结构的变化如何影响酸化机制和系统特异性.
主要方法:
- 利用AlphaFold准确预测各种HKs的二维结构,区分cis和trans配置.
- 模拟多个HK以评估酸化机制的进化分布.
- 分析了结构特征,特别是围绕二分化和酸化 (DHp) 域的螺旋长度,以确定酸化机制的决定因素.
主要成果:
- AlphaFold准确地预测了HK是否在cis或trans形态中进行二元化.
- 无论是cis-还是trans-acting HKs在自然界中都是普遍存在的,观察到的机制之间存在多个进化开关.
- 沿着DHp循环的螺旋长度的差异被确定为酸化机制的关键分子决定因素.
- 这些螺旋体的微小结构变化可以诱导酸化机制的切换.
结论:
- 在HKs中的酸化机制在结构上是由周围螺旋体的长度决定的.
- 进化分析显示 cis 和 trans 机制之间的频繁切换,表明它们在途径分歧中的作用.
- 在特定的HK中保存的酸化机制表明它们在维持系统特异性的重要性,而切换允许适应和多样化.
相关概念视频
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
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
Allosteric Proteins-ATCase
5.7K
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...
5.7K
Amplifying Signals via Enzymatic Cascade
8.5K
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...
8.5K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K


