在CMKLR1的循环化学素-9和化学素S157蛋白的结合方式
Tina Schermeng1, Fabian Liessmann2,3, Carla Katharina Ambrosius1
1Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Brüderstraße 34, 04103, Leipzig, Germany.
Chembiochem : a European journal of chemical biology
|October 18, 2024
概括
研究人员模拟了化学类受体1 (CMKLR1) 与化学变体的相互作用. 计算和实验数据显示了化学S157和循环化学S-9 (cC9) 的独特结合模式,有助于未来的药物设计.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 化基因类受体1 (CMKLR1) 是由阿迪波金化学素激活的.
- 之前的研究揭示了化学素-9与CMKLR1-Gi.结合的冷EM结构.
- 化学素-9是一种非,表现出类似的Ca2+释放活性,但与全长化学素相比,不同的平衡读数.
研究的目的:
- 通过计算建模CMKLR1并研究循环化学素-9 (cC9) 和化学素S157.7的结合模式.
- 为了比较cC9和chemerinS157与CMKLR1的结合相互作用,相对于chemerin-9.
- 为了确定关键的残留物和相互作用,涉及到带结合到CMKLR1.1.
主要方法:
- 对CMKLR1.1进行计算建模.
- 分析CMKLR1变体和双突变周期分析.
- 计算预测的实验验证,包括功效测量 (pEC50).
主要成果:
- 双突变周期分析发现CMKLR1-F2.53对于cC9.9的Phe8结合至关重要.
- 在第8位使用1 - 纳菲尔-L-alanine的chemerin-9变体显示出强度增加了4倍 (pEC50=8.6±0.15).
- 一个计算模型表明CMKLR1和chemerinS157之间的β-sheet相互作用,经过实验证实.
结论:
- 化学素9和cC9在CMKLR1共享结合相互作用,而化学素S157在深结合部位容忍更多的突变.
- 该研究确定了CMKLR1.1中化学素S157和cC9的独特结合方式.
- 这些发现有助于未来以结构为基础的药物设计,针对CMKLR1.
相关概念视频
01:27Chemotaxis in E. coli
3
Chemotaxis in Escherichia coli is a sensory-driven motility mechanism that enables bacteria to navigate chemical gradients, moving toward beneficial environments while avoiding harmful conditions. This process relies on a signal transduction system integrating external chemical cues with flagellar motor control.Chemoreceptors and Signal DetectionE. coli detects chemical gradients through methyl-accepting chemotaxis proteins (MCPs), which are membrane-bound chemoreceptors that sense attractants...
3
01:16Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
01:25Structure of Cadherins
3.3K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
3.3K
00:49Ligand 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